CRISPR may introduce hundreds of unwanted mutations into the genome, a small study finds.

Until now, 'off-target effects' of the CRISPR/Cas9 system were thought to be minimal, with improvements to the technique reducing errors to nearly undetectable levels. However, now a new study suggests previous methods for detecting off-target mutations may have underestimated the true scale of unwanted effects.

'We feel it's critical that the scientific community consider the potential hazards of all off-target mutations caused by CRISPR,' said co-author Dr Stephen Tsang, from Columbia University Medical Centre, New York. 'Researchers who aren't using whole genome sequencing to find off-target effects may be missing potentially important mutations. Even a single nucleotide change can have a huge impact.'

The precise nature of CRISPR has contributed to its growing popularity in recent years. Yet until now, researchers have been using computer algorithms to check the accuracy of the technique,by identifying and scanning regions of the genome most likely to be affected by genome editing.

'These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals,' said co-author Dr Alexander Bassuk at the University of Iowa.

In a previous study, the team had used CRISPR in two mice to correct a faulty gene that causes blindness. In their new study, published in Nature Methods, the researchers compared the genomes of the edited mice to a single non-edited control mouse.

They found over 1500 single-nucleotide mutations and over 100 larger deletions or insertions in the two CRISPR mice. In spite of this, the mice appeared healthy and did not show any obvious side effects due to the off-target mutations.

Some experts in the field are sceptical of the findings, raising concerns over the experimental design of the study. Dr Gatan Burgio from the Australian National University, Canberra, whose research group has a keen interest in CRISPR genome-editing technologies, stated to Medium:'I would predict very few if not close to none of these variants are CRISPR related.' Instead he believes a number of issues with the methodology, as well as the small sample size, can explain the 'abnormal number of mutations'. Further investigation by other research groups will be needed to validate these results and determine the future implications for CRISPR methods.

The first CRISPR clinical trial in patients already underway in China and another is expected to start in the US in the next year.

The researchers say they hope other groups will use their methods to assess off-target mutations and improve the accuracy of CRISPR.

'We're still upbeat about CRISPR,' said co-author Dr Vinit Mahajan at Stanford University. 'We're physicians, and we know that every new therapy has some potential side effects - but we need to be aware of what they are.'

Originally posted here:

CRISPR genome editing may cause unintended mutations - BioNews

Recommendation and review posted by Bethany Smith

A consultant studies a mammogram. The drug olaparib could slow cancer growth by three months, researchers have found. Photograph: Rui Vieira/PA

A type of inherited and incurable breast cancer that tends to affect younger women could be targeted by a new gene therapy, researchers have found.

A small study presented at the worlds largest cancer conference found treating patients with the drug olaparib could slow cancer growth by three months and be less toxic for patients with inherited BRCA-related breast cancer.

Researchers said there was not enough data to say whether patients survived longer as a result of the treatment.

We are in our infancy, said Dr Daniel Hayes, president of the American Society of Clinical Oncology and professor of breast cancer research at the University of Michigan. This is clearly an advance; this is clearly proof of concept these can work with breast cancer.

Does it look like its going to extend life? We dont know yet, he said.

The drug is part of the developing field of precision medicine, which targets patients genes to tailor treatment.

It is a perfect example of how understanding a patients genetics and the biology of their tumor can be used to target its weaknesses and personalize treatment, said Andrew Tutt, director of the Breast Cancer Now Research Centre at The Institute of Cancer Research.

Olaparib is already available for women with BRCA-mutant advanced ovarian cancer, and is the first drug to be approved that is directed against an inherited genetic mutation. The study was the first to show olaparib can slow growth of inherited BRCA-related breast cancer. The drug is not yet approved for that use.

People with inherited mutations in the BRCA gene make up about 3% of all breast cancer patients, and tend to be younger. The median age of women in the olaparib trial was 44 years old.

BRCA genes are part of a pathway to keep cells reproducing normally. An inherited defect can fail to stop abnormal growth, thus increasing the risk of cancer. The study examined the effectiveness of olaparib against a class of BRCA-related cancers called triple negative. Olaparib is part of a class of four drugs called PARP-inhibitors that work by shutting down a pathway cancer cells use to reproduce.

The study from Memorial Sloan Kettering Cancer Center in New York randomly treated 300 women with advanced, BRCA-mutated cancer with olaparib or chemotherapy. All the participants had already received two rounds of chemotherapy.

About 60% of patients who received olaparib saw tumors shrink, compared with 29% of patients who received chemotherapy. That meant patients who received olaparib saw cancer advance in seven months, versus four months for only chemotherapy.

Researchers cautioned it is unclear whether olaparib extended life for these patients, and that more research was needed to find out which subset of patients benefit most from olaparib.

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New gene therapy offers hope against incurable form of breast cancer - The Guardian

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Scientists in Australia claim to have discovered what could be a life-long cure for potentially fatal allergies to peanuts, shellfish and other food.

The researchers said they had been able to turn off the allergic response in tests on mice using gene therapy to desensitise the bodys immune system, and suggested this could also be used to treat asthma.

They predicted human trials could begin in just five or six years.

Commenting on the study, a leading British expert said scientists had managed to cure allergies in mice before without this leading to an effective human treatment, but added that the new research could lead to the "Holy Grail" of allergy treatment.

He was sceptical about the researchers' claims their technique might be effective against asthma, but Asthma UK said it was "a very exciting step forward".

Allergies occur when the immune system over-reacts to something that is usually harmless. In the journal JCI Insight, the Australian researchers reported they had used genetic techniques to prevent this from happening in mice who were allergic to the protein in egg whites.

In a video about the new research, Professor Ray Steptoe, of Queensland University, said: We can actually turn off the response. What that means is the disease is stopped in its tracks.

What we do is we stop the underlying disease that causes these symptoms. That could revolutionise treatment for severe allergies. It would prevent, we think, some of the life-threatening allergic episodes that occur for people who are allergic to foods for instance.

That would make a huge difference for people with severe allergies what that would mean is they would no longer be in fear of life-threatening incidents if they were to go to a restaurant and be exposed to shellfish and they werent aware that was in the food.

Kids with peanut allergies could go to school without any fear of being contaminated from other kids food.

We envisage in the future, with this approach, that they could go to the doctors rooms, get a single treatment and that would give them permanent protection from future allergic attacks or asthma attacks.

He added that the researchers hoped human trials could begin in five to six years, estimated it would take a similar period after that for the treatment to be available to patients.

Professor Adnan Custovic, an allergy expert at Imperial College London, expressed particular caution about the claim the treatment would be effective against asthma as the condition is caused by a completely different mechanism to the one behind food allergies.

But he added: This is one of the potentially exciting approaches to treating allergies.

Its sort of approach, where you try to switch off the allergic response, is kind of the Holy Grail, but a mouse model is not the same as a human model.

We can cure allergies in mice but we cannot do it in humans the mechanisms are not identical. Only time will tell whether this approach will be a viable one.

And he criticised the degree of optimism about the technique expressed by the Australian team.

My real problem with this sort of bombastic statements like this is people with asthma it gives them hope which very often is not realistic, Professor Custovic said.

However Dr Erika Kennington, head of research at Asthma UK, was more optimistic.

This is potentially a very exciting step forward in asthma research," she said.

"Allergen immunotherapy exposing people to small amounts of an allergen in order to build up tolerance is currently the only disease-altering treatment available for asthma but it can have significant side effects in some people, and every other existing asthma treatment and medication works by reducing or relieving the symptoms.

"These findings suggesting a novel approach to reversing allergic disease are therefore very welcome.

We also know that there are certain allergy triggers that cause asthma flare ups, which makes this research important in possibly reducing the risk of life-threatening asthma attacks."

But Dr Kennington also pointed to the difference between animal and human trials.

A lot more research is needed to see if the same results can be achieved in people before we can say that a cure for asthma is around the corner," she said.

In the study of the allergic mice, the researchers inserted a gene into blood stem cells that controls the immune response to the egg white.

The genetically modified cells were then injected into the mices bone marrow, where they produced new blood cells that were able to turn off the allergic response.

The researchers hope to create a similar form of gene therapy that works on humans after a single injection.

We havent quite got it to the point where its as simple as getting a flu jab, so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals, Dr Steptoe said.

Dr Louisa James, British Society for Immunology spokesperson and an immunologistat Queen Mary University of London, said allergies were "far more complex than can be replicated in an animal model".

"Patients with severe allergies often react to several different types of allergen and symptoms can develop over several years," she said.

"Although the results are encouraging and heading in the right direction, it is too early to predict whether this form of therapy could ever be used to treat allergies in humans.

"As the authors state in their paper 'gene-therapy is not yet suitable for clinical application to mild disease in young individuals'.

"There are simply too many open questions around the translation of these findings from animal models into humans.Would the cells engineered to produce allergens produce the same response in humans? How would other immune cells that play a critical role in human allergy be affected? What are the mechanisms that switch off the immune response and are they comparable in humans?

This approach holds promise, and further research is certainly warranted, but claims that a single injection could switch off allergies are over-optimistic at this time.

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Allergy treatment: Scientists claim breakthrough that could lead to ... - The Independent

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The team hopes to develop a single, injected, gene therapy treatment that could eliminate many severe allergic responses (Credit: University of Queensland)

Scientists may be one step closer to discovering a way to genetically "turn off" allergic responses with a single injection. A team of researchers at the University of Queensland has developed a new process that has successfully silenced a severe allergic response in mice, using blood stem cells engineered with a gene that can target specific immune cells.

The big challenge previous allergy researchers faced was that immune cells, known as T-cells, tended to develop a form of "memory" so that once someone developed an immune response to an allergen, it would easily recur upon future contact. The key was finding a way to erase that "memory" response to the protein in the allergen causing the immune reaction.

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"We take blood stem cells, insert a gene which regulates the allergen protein and we put that into the recipient," says Professor Ray Steptoe, explaining the new process developed by his team at The University of Queensland. "Those engineered cells produce new blood cells that express the protein and target specific immune cells, 'turning off' the allergic response."

The team's initial clinical investigations looked at an experimental asthma allergen, with the new process found to successfully terminate established allergic responses in sensitized laboratory mice. While the initial research has focused on a very specific asthma allergen, Professor Steptoe believes the process could be applied to many other severe allergic responses, such as peanuts, bee venom and shell fish.

The long-term goal of the research would be to develop a therapy that could cure specific allergies with a single injection, much like a vaccine.

"We haven't quite got it to the point where it's as simple as getting a flu jab," says Professor Steptoe, "so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals."

The team is realistic about the time it will take before this discovery results in practical benefits for allergy sufferers, with at least five years more laboratory work needed before even human trials can be conducted. But this new discovery could mean that, within 10 or 15 years, asthma and other lethal allergic responses might be eliminated with a single, one-time treatment.

The findings were recent published in the journal JCI Insight.

Watch Professor Ray Steptoe from The University of Queensland discuss his team's findings in the video below.

Source: The University of Queensland

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Gene therapy could wipe immune memory and "turn off" severe allergies - New Atlas

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RenovaCare is developing breakthrough technologies to address Americas $45 billion wound and burn treatment market. Our flagship CellMist System makes use of a patients own stem cells, which are sprayed onto wounds using our novel SkinGun device.

For patients suffering severe burns and other wounds, the prospect of a quick-healing, gentle spray containing their own stem cells will be a promising alternative to conventional skin graft surgery, which can be painful, prone to complications, and slow-to-heal. Based on preliminary case studies, CellMist System patients can be treated within 90 minutes of arriving in an emergency room; a patients stem cells are isolated, processed, and sprayed on to wound sites for rapid healing.

Preliminary investigational use in Europe and the United States indicate the potential efficacy and safety of RenovaCares technologies. Clinical observations point to the potential for regeneration of new skin in as little as four days, rather than the many weeks of painful and risky recovery required by traditional skin graft techniques. These technologies are the result of nearly a decade of ongoing research and development dedicated to finding the most effective way to access the regenerative properties of a patients own skin stem cells, and the most efficient way to deliver these potent cells to heal moderate to severe skin wounds. We believe that RenovaCares CellMist System and SkinGun spray device are the worlds most advanced technologies of their kind.

This device system requires further clinical evaluation and data collection prior to submission of a premarketing application to the US FDA. At this time it is an investigational system and is not available for general use or sales in the United States.

The CellMist System RenovaCares CellMist System is comprised of two components:

Wikipedia indicates that so far the skin gun treatment has been used exclusively with second degree burns, though there is strong evidence that the treatment will be successful in treating a variety of skin wounds and skin disorders. Patients with infected wounds or with delay in wound healing are suitable for cell grafting treatment. Third-degree burns, however, completely deprive victims of both their epidermis and dermis skin levels, which exposes the tissue surrounding the muscles. The skin gun has not progressed to the point where it can be used for such advanced wounds, and these patients must seek more traditional treatment methods. The skin gun is generally not used for burn victims with anything less than a second-degree burn either. First degree-burns still maintain portions of the epidermis and can readily heal on their own, thus they do not need this expensive technology.

Currently, the skin guns applications have not been extended to include the regeneration of skin lost due to other injuries or skin diseases. It is also limited in that it is only effective immediately following the burn incident.

The average healing time for patients with second degree burns is three to four weeks. This is reduced to a matter of days with skin gun treatment

Traditional skin grafting can be risky, in that chances for infection are relatively high. The skin gun alleviates this concern because the increased speed in which the wound heals directly correlates to the decreased time the wound can be vulnerable to infection. Because of the rapid re-epithelialization associated with skin gun treatment, harmful side effects that can result from an open wound are significantly reduced. Applying the skin cells is quick and doesnt harm the patient because only a thin layer of the patients healthy skin is extracted from the body into the aqueous spray. The electronic spray distributes the skin cells uniformly without damaging the skin cells, and patients feel as if they are sprayed with salt water.

Because the skin cells are actually the patients own cells, the skin that is regenerated looks more natural than skin grown from traditional methods. During recovery, the skin cells grow into fully functional layers of the skin, including the dermis, epidermis, and blood vessels.[17] The regenerated skin leaves little scarring. The basic idea of optimizing regenerative healing techniques to damaged biological structures demonstrated by the skin gun in the future may also be applied to engineering reconstruction of vital organs, such as the heart and kidneys.

There are major limitations: the method will not work on deep burns that go through bone and muscle, specifically below the dermis. As of 2011, only several dozen patients have been treated; it remains an experimental, not a proven, method. As of 2011, the skin gun was still in its prototyping stage, since it has only treated a dozen patients in Germany and the US, compared to over 50,000 treated with Dermagraft bioengineered skin substitute. There is thus a lack of published peer reviewed clinical evidence, and no knowledge of long-term stability of the newly generated skin

Skingun Procedure

There is a seven page review of the skingun at the International Journal of Pharmacometrics and Integrated Biosciences (IJPIB)

Skingun Procedure Initially stamp-sized healthy skin of the injured patient is taken and stem cells were collected from it. Then they are harvested by using suitable enzymes. The prepared cell suspension is injected into sterile syringe and inserted into the gun. This gun helps in uniform spreading of the cells on wound. These cells will migrate, multiple, and differentiate forming a new tissue. The complete process occurs with in 2 hr. Full regeneration of skin occurs in 2 weeks and complete formation of texture tools 2-3 months

Stage 1

The CellMist Solution is a liquid suspension containing a patients own regenerative skin stem cells. A small sample (as little as a square inch) of the patients skin is quickly processed to liberate the stem cells from surrounding tissue. The resulting product is referred to as the CellMist Solution. The CellMist Solution is placed in the SkinGun for spray application onto the patients wound.

The CellMist Solution, containing the patients stem cells, is transferred to the SkinGun. The SkinGun sprays the cells onto wound sites to begin healing. Unlike conventional aerosol and pump systems, our next-generation fluid sprayer does not expose fragile cells to strong forces that can tear them apart. Instead our SkinGun gently delivers the CellMist Solution directly to the wound site using a positive-pressure air stream.

SOURCES RenovaCare, Wikipedia, International Journal of Pharmacometrics and Integrated Biosciences (IJPIB)

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Stem cells delivered via Skin gun can reduce second degree ...

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Tissue-specific stem cells

Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found

Stem cells are the foundation cells for every organ and tissue in our bodies. The highly specialized cells that make up these tissues originally came from an initial pool of stem cells formed shortly after fertilization. Throughout our lives, we continue to rely on stem cells to replace injured tissues and cells that are lost every day, such as those in our skin, hair, blood and the lining of our gut. Stem cells have two key properties: 1) the ability to self-renew, dividing in a way that makes copies of themselves, and 2) the ability to differentiate, giving rise to the mature types of cells that make up our organs and tissues.

Tissue-specific stem cells Tissue-specific stem cells, which are sometimes referred to as adult or somatic stem cells, are already somewhat specialized and can produce some or all of the mature cell types found within the particular tissue or organ in which they reside. Because of their ability to generate multiple, organ-specific, cell types, they are described as multipotent. For example, stem cells found within the adult brain are capable of making neurons and two types of glial cells, astrocytes and oligodendrocytes. Tissue-specific stem cells have been found in several organs that need to continuously replenish themselves, such as the blood, skin and gut and have even been found in other, less regenerative, organs such as the brain. These types of stem cells represent a very small population and are often buried deep within a given tissue, making them difficult to identify, isolate and grow in a laboratory setting. Neuron Dr. Gerry Shaw, EnCor Biotechnology Inc. Astrocyte Abcam Inc. Oligodendrocyte Dhaunchak and Nave (2007). Proc Natl Acad Sci USA 104:17813-8 http://www.isscr.org Embryonic stem cells Embryonic stem cells have been derived from a variety of species, including humans, and are described as pluripotent, meaning that they can generate all the different types of cells in the body. Embryonic stem cells can be obtained from the blastocyst, a very early stage of development that consists of a mostly hollow ball of approximately 150-200 cells and is barely visible to the naked eye. At this stage, there are no organs, not even blood, just an inner cell mass from which embryonic stem cells can be obtained. Human embryonic stem cells are derived primarily from blastocysts that were created by in vitro fertilization (IVF) for assisted reproduction but were no longer needed. The fertilized egg and the cells that immediately arise in the first few divisions are totipotent. This means that, under the right conditions, they can generate a viable embryo (including support tissues such as the placenta). Within a matter of days, however, these cells transition to become pluripotent. None of the currently studied embryonic stem cell lines are alone capable of generating a viable embryo (i.e., they are pluripotent, not totipotent). Why are embryonic stem cells so valuable? Unlike tissue-specific (adult) stem cells, embryonic stem cells have the potential to generate every cell type found in the body. Just as importantly, these cells can, under the right conditions, be grown and expanded indefinitely in this unspecialized or undifferentiated state. These cells help researchers learn about early human developmental processes that are otherwise inaccessible, study diseases and establish strategies that could ultimately lead to therapies designed to replace or restore damaged tissues. Induced pluripotent stem cells One of the hottest topics in stem cell research today is the study of induced pluripotent stem cells (iPS cells). These are adult cells (e.g., skin cells) that are engineered, or reprogrammed, to become pluripotent, i.e., behave like an embryonic stem cell. While these iPS cells share many of the same characteristics of embryonic stem cells, including the ability to give rise to all the cell types in the body, it is important to understand that they are not identical. The original iPS cells were produced by using viruses to insert extra copies of three to four genes known to be important in embryonic stem cells into the specialized cell. It is not yet completely understood how these three to four reprogramming genes are able to induce pluripotency; this question is the focus of ongoing research. In addition, recent studies have focused on alternative ways of reprogramming cells using methods that are safer for use in clinical settings. Disease- or patient-specific pluripotent stem cells One of the major advantages of iPS cells, and one of the reasons that researchers are very interested in studying them, is that they are a very good way to make pluripotent stem cell lines that are specific to a disease or even to an individual patient. Disease-specific stem cells are powerful tools for studying the cause of a particular disease and then for testing drugs or discovering other approaches to treat or cure that disease. The development of patientspecific stem cells is also very attractive for cell therapy, as these cell lines are from the patient themselves and may minimize some of the serious complications of rejection and immunosuppression that can occur following transplants from unrelated donors. Moving stem cells into the clinic Clinical translation is the process used to turn scientific knowledge into real world medical treatments. Researchers take what they have learned about how a tissue usually works and what goes wrong in a particular disease or injury and use this information to develop new ways to diagnose, stop or fix what goes wrong. Before being marketed or adopted as standard of care, most treatments are tested through clinical trials. Sometimes, in attempting new surgical techniques or where the disease or condition is rare and does not have a large enough group of people to form a clinical trial, certain treatments might be tried on one or two people, a form of testing sometimes referred to as innovative medicine. For more information on how science becomes medicine, please visit http://www.closerlookatstemcells.org. Current therapies Blood stem cells are currently the most frequently used stem cells for therapy. For more than 50 years, doctors have been using bone marrow transplants to transfer blood stem cells to patients, and more advanced techniques for collecting blood stem cells are now being used to treat leukemia, lymphoma and several inherited blood disorders. Umbilical cord blood, like bone marrow, is often collected as a source of blood stem cells and in certain cases is being used as an alternative to bone marrow transplantation. Additionally, some bone, skin and corneal diseases or injuries can be treated by grafting tissues that are derived from or maintained by stem cells. These therapies have also been shown to be safe and effective. Potential therapies Other stem cell treatments, while promising, are still at very early experimental stages. For example, the mesenchymal stem cell, found throughout the body including in the bone marrow, can be directed to become bone, cartilage, fat and possibly even muscle. In certain experimental models, these cells also have some ability to modify immune functions. These abilities have created considerable interest in developing ways of using mesenchymal stem cells to treat a range of musculoskeletal abnormalities, cardiac disease and some immune abnormalities such as graft-versus-host disease following bone marrow transplant. Remaining challenges Despite the successes we have seen so far, there are several major challenges that must be addressed before stem cells can be used as cell therapies to treat a wider range of diseases. First, we need to identify an abundant source of stem cells. Identifying, isolating and growing the right kind of stem cell, particularly in the case of rare adult stem cells, are painstaking and difficult processes. Pluripotent stem cells, such as embryonic stem cells, can be grown indefinitely in the lab and have the advantage of having the potential to become any cell in the body, but these processes are again very complex and must be tightly controlled. iPS cells, while promising, are also limited by these concerns. In both cases, considerable work remains to be done to ensure that these cells can be isolated and used safely and routinely. Second, as with organ transplants, it is very important to have a close match between the donor tissue and the recipient; the more closely the tissue matches the recipient, the lower the risk of rejection. Being able to avoid the lifelong use of immunosuppressants would also be preferable. The discovery of iPS cells has opened the door to developing patient-specific pluripotent stem cell lines that can later be developed into a needed cell type without the problems of rejection and immunosuppression that occur from transplants from unrelated donors. Third, a system for delivering the cells to the right part of the body must be developed. Once in the right location, the new cells must then be encouraged to integrate and function together with the bodys other cells. http://www.isscr.org Glossary Blastocyst A very early embryo that has the shape of a ball and consists of approximately 150-200 cells. It contains the inner cell mass, from which embryonic stem cells are derived, and an outer layer of cells called the trophoblast that forms the placenta. Cell line Cells that can be maintained and grown in a dish outside of the body. Clinical translation The process of using scientific knowledge to design, develop and apply new ways to diagnose, stop or fix what goes wrong in a particular disease or injury. Differentiation The process of development with an increase in the level of organization or complexity of a cell or tissue, accompanied by a more specialized function. Embryo The early developing organism; this term denotes the period of development between the fertilized egg and the fetal stage. Embryonic stem cell Cells derived from very early in development, usually the inner cell mass of a developing blastocyst. These cells are self-renewing (can replicate themselves) and pluripotent (can form all cell types found in the body). Induced pluripotent stem (iPS) cell Induced pluripotent cells (iPS cells) are stem cells that were engineered (induced) from non-pluripotent cells to become pluripotent. In other words, a cell with a specialized function (for example, a skin cell) that has been reprogrammed to an unspecialized state similar to that of an embryonic stem cell. Innovative medicine Treatments that are performed on a small number of people and are designed to test a novel technique or treat a rare disease. These are done outside of a typical clinical trial framework. In vitro fertilization A procedure in which an egg cell and sperm cells are brought together in a dish to fertilize the egg. The fertilized egg will start dividing and, after several divisions, forms the embryo that can be implanted into the womb of a woman and give rise to pregnancy. Mesenchymal stem cells Mesenchymal stem cells were originally discovered in the bone marrow, but have since been found throughout the body and can give rise to a large number of connective tissue types such as bone, cartilage and fat. Multipotent stem cells Stem cells that can give rise to several different types of specialized cells, but in contrast to a pluripotent stem cell, are restricted to a certain organ or tissue types. For example, blood stem cells are multipotent cells that can produce all the different cell types that make up the blood but not the cells of other organs such as the liver or brain. Pluripotent stem cells Stem cells that can become all the cell types that are found in an implanted embryo, fetus or developed organism. Embryonic stem cells are pluripotent stem cells. Self-renewal The process by which a cell divides to generate another cell that has the same potential. Stem cells Cells that have both the capacity to self-renew (make more stem cells by cell division) and to differentiate into mature, specialized cells. Tissue-specific stem cells (also known as adult or somatic stem cells) Stem cells found in different tissues of the body that can give rise to some or all of the mature cell types found within the particular tissue or organ from which they came, i.e., blood stem cells can give rise to all the cells that make up the blood, but not the cells of organs such as the liver or brain. Totipotent stem cells Stem cells that, under the right conditions, are wholly capable of generating a viable embryo (including the placenta) and, for humans, exist until about four days after fertilization, prior to the blastocyst stage from which embryonic stem cells are derived.

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What Are Stem Cells - Checkbiotech.org (press release)

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Slide: 1 / of 1. Caption: Getty Images

When it comes toCrispr, the bacterial wnderenzyme that allows scientists to precisely edit DNA, no news is too small to stir up some drama. On Tuesday morning, doctors from Columbia, Stanford, and the University of Iowa published a one-page letterto the editor of Nature Methodsan obscure but high-profile journaldescribing something downright peculiar. About a year ago, they used Crispr to edit out a blindness-causing genetic defect in mice, curing two of their cohort. Later, they decided to go back and sequence their genomes, just to see what else Crispr did while it was in there.

A lot, it turned out. With their method, the researchers observed close to 2,000 unintended mutations throughout each mouses genome, a rate more than 10 times higher than anyone had previously reported. If that holds up, Crispr-based therapies are in for some serious trouble. No one wants to go in for a vision-restoring treatment, only to wind up with cancer because of it.

The ensuing headlines were gleefully apocalyptic: Crispr May Not Be Nearly as Precise as We Thought, Crack in Crispr Facade after Unanticipated In Vivo Mutations Arise, and my personal favorite, Small Study Finds Fatal Flaw in Gene Editing Tool Crispr. And then the biotech stocks went into a tailspin. The big three Crispr-based tech companies got hit the hardest. By the close of trading Tuesday, Editas Medicine was down nearly 12 percent, Crispr Therapeutics fell more than 5 percent, and Intellia Therapeutics had plunged to just over 14 percent.

This was far from just a blip in the nerdy news cycle. A reaction to a single scientific publication on this scale raises important questions about sciences incentive structure, its processes for publicly evaluating evidence, and what happens when those butt up against the prevailing philosophies of other professionsnamely, medicine.

A decade ago, most of the conversations about this letter would have happened in laboratory hallways. But this week, geneticists, microbiologists, and molecular bioengineers took to Twitter to digest the paper in public. While some experts decried the paper as unnewsworthy (everyones known about Crispr off-target mutations forever!) the majority of threads ticked off the experiments flaws: Tiny sample size! Insufficient controls! Weird Crispr delivery! Out of date/inefficient version of Crispr! The list goes on. Many doubted if it had been peer-reviewed. (It had.) The hashtag #fakenews even made a few appearances.

To be sure, the results do not match up well with whats already in the literature on this subject. And, as the paper itself says, The unpredictable generation of these variants is of concern. Which is to say, the authors have no idea why or how these mutations are happening. Derek Lowe, a longtime pharmaceutical industry researcher who writes a blog on the subject for Science, had enough doubt in the results that he bought up some Editas and Crispr Therapeutics stocks while they were down.

But most scientists, while skeptical of the results, were more disappointed in the way the paper was blown out of proportion. Its critically important to look closely at genomes being edited with the Crispr system, ideally with a method sensitive enough to detect even rare off-target events, says Stephen Floor, a biophysicist who worked in Crispr creator Jennifer Doudnas lab at UC Berkeley before beginning his own gene editing cancer research at UCSF. Saying Crispr is 100 percent accurate or grossly inaccurate isnt helpful. What scientists need to understand is which sites are being cut, what rules govern which sites get cut, and how to emphasize only cutting at sites you want. It will be interesting to watch subsequent validation that gets to the bottom of why this report found such a surprisingly high rate of mutation, he says.

The key word there, if you didnt catch it, is validation. Its pretty much the foundational tenet of science. You have an idea, you test it, you test it again, you eliminate confounding factors as best as you can and then you validate your results. All the critiques of the Nature Methods paper assumed the authors were operating with that same premise.

But in this case, the authors werent scientists: They were doctors. And in medicine, theres a different guiding principle that places a premium on sharing significant results at face value.

The history of the case study is long and celebrated in medicine. The first recorded report of what would one day be known as HIV/AIDS was published by the CDC as five strange cases of pneumonia in gay men in Los Angeles. Vinit Majahan, an opthamologist at Stanford and co-author of Tuesdays Crispr paper, says it was in that spirit that he and his collaborators submitted their results to the journal. I dont have any money in Crispr, I only have patients, he says. The culture and pressures of science right now push people to not share results that arent a splashy cure. But in medicine you cant do that. If you make an observation thats important enough to share with your community, youre obligated to do that right away.

Since Majahans team is working on turning its previous work into a human treatment, they saw it as irresponsible to take their results, small as they were, and sweep them under the rug. Crispr is most often described as molecular scissors, but doctors like Majahan tend to think of it more like a drug. And the more successes Crispr haslike curing mouse blindnessthe more doctors start asking the next logical questions about things like dosing and formulations and side effects. How long can you have the enzyme floating around your cells before it cuts somewhere it shouldnt? Whats the right enzyme for the job?

Matthew Taliaferro, who studies gene expression and gene editing at MIT, thinks the paper will get more scientists thinking about those kinds of questions. Crispr definitely has off-targets. But a lot of people use it assuming no other mutations get introduced during the process, he says. So getting people to talk about the need for controls is a good outcome of this whole thing. And while he was surprised by the lack of some straightforward controls, Taliaferro is awarethat his initial reactions were colored by some of the Twitter threads hed already absorbed before tracking down the paper himself. I think the data is perfectly fine, he says. Its just the interpretation of it that to me seems odd. Namely, that every Crispr application is deeply flawed.

Which was never Majahans intention in the first place. We didnt write the headlines, he says. We dont think Crispr is bad, we think its great. But he didnt get the opportunity to tell people that, because for one thing, hes not on Twitter. When asked how he was responding to the criticisms from the scientific community, he laughed and said, Can you read some to me? Ive heard theres some nasty stuff out there.

The amplifications (and denigrations) of those interpretations around Science Twitter may not have been as knee-jerk as all the Crispr Is Terrible and Broken Forever headlines. But still, they were an overreactionbecause after all, this was just a single paper. No one should presume a standalone study can predict the future of an entire technique. At most, it indicates that Crispr is entering its inevitable adolescence, when shiny silver bullet technologies get banged up and battle worn by new data. That doesnt mean it isnt the real deal. Just that it should be looked at real hard every step of the way.

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Crispr's Next Big Debate: How Messy Is Too Messy? - WIRED

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For the past few years, CRISPR has constantly been in the spotlight for a myriad of reasons. In addition to the rapid advancements in the technology and its expanding applications, umpteen number of news stories have covered the battle for the patent between competing groups. Whether we talk about benignmosquitoes that do not transmit malaria or extraordinarily muscular beaglesormini pigs, CRISPR is everywhere and everyone is using it.

CRISPR is a natural adaptation found in bacteria which allows it to defend itself from invading bacteriophages. The host bacteria creates a memory of the invading bacteriophage DNA sequence in its own genome. This serves as a memory that can be used to cleave specific DNA sequences of invading organisms by the cleavage enzyme Cas9 in the event of an infection. Scientists have been able to use this ability of the Cas9 enzyme to undertake targeted gene editing inin vitroas wellasin vivomodel systems.

Last year backed by the venture capitalist Sean Parker, The National Institute of Health approved a proposal for human clinical trials of CRISPR. Taking it one step ahead, Chinese oncologists at Sichuan University injected CRISPR-Cas9 modified cells in a patient suffering from an aggressive form of lung cancer in October last year.Despite the ease of use offered by CRISPR to completely ablate gene expression, there have been concerns regarding the specificity and efficiency in practice.

A recent study revealing several unexpected mutationsafter CRISPR-Cas9 editing in vivohas set alarm bells ringing.

A team of researchers in the US set out to repair a genetic mutation known to cause blindness in mice. Using CRISPR gene editing, they were able to successfully correct the targeted mutation in each of the two mice they treated. In a later study, the team sequenced the entire genome of two mice that had undergone CRISPR gene editing, and one healthy control. They observed an alarming number of additional DNA changes more than 1,600 per mouse in areas of the genome they did not intend to modify. Researchers in the past used computer algorithms to identify and examine areas most likely to be affected by off-target mutations.

These predictive algorithms seem to do a good job when CRISPR is performed in cells or tissues in a dish, but whole genome sequencing has not been employed to look for all off-target effects in living animals Alexander Bassuk, team member, University of Iowa.

Researchers who arent using whole genome sequencing to find off-target effects may be missing potentially important mutations, even a single nucleotide change can have a huge impact.- Dr. Tsang

This new piece of information from Schaefer et alcomes at a crucial moment in time as regulatory bodies across the world are getting ready to approve CRISPR-based therapies. Whole genome sequencing could be an important emerging benchmark for approved CRISPR therapies.

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How many is one too many? Off target mutations in CRISPR reported by whole genome sequencing - Biotechin.Asia

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ELKTON I spent a fair amount of time in cemeteries last week, said Cuffs, explaining his recent absence from the local scene. Attending memorial services and visiting relatives graves.

Billy Bibbs and I nodded, encouraging the North Street Hotel curmudgeon to continue his report.

Peaceful places, Cuffs added. Usually pretty empty except on weekends and holidays. But during the workweek you might see a few workers doing landscaping and general maintenance. Opening up fresh graves for upcoming funerals.

Allows you plenty of privacy, and time to reflect upon your loved ones. Even talk out loud if you want. Nobody around to overhear your private thoughts.

Well, Bibbs said, that old fashioned burial-in-the-ground routine aint for me. Im going to get myself cremated. Save on cost, less aggravation to deal with, and no need to buy a clean white shirt and new suit plus Ill be doing my part to help the environment.

I nodded, offering no comment. I didnt care if Bibbs was tossed off the side of his crab boat into the upper Chesapeake, given a dirt nap in a county boneyard, or cooked to a crisp and had his ashes jammed in a jelly jar.

Cuffs thought differently, however, saying, You might want to think about donating your sorry stupid self to science, he said, sporting a smile. Maybe then some clumsy med student could look inside your thick skull and see what wires are crossed. Then wed find out why you were such a pain in all our backsides.

Jimmy, the saloons owner, happened to be passing by, and entered the conversation with a question: Have you ever heard of anybodys body being rejected for scientific study? From what I understand, years ago it was against the law. But now I hear they take everybody and anybody.

I couldnt resist, So that gives Bibbs two options. He can finally become some use to society as a scientific case study. Or spend the hereafter in a fancy vase, perched on somebodys bookshelf.

Id rather be scattered across the finish line at Delaware Park, Bibbs said. In fact, I think Ill make sure thats written down in my will.

Everyone enjoyed his remark, but when the laughter died down, Cuffs said, This cremation thing got me to thinking, so I did a bit of research.

Look out, said Jimmy, sounds like were moving into serious territory.

Did you know, Cuffs said, there are thousands. Maybe tens of thousands, of unclaimed cremated remains stacked in storage areas in funeral parlors across the country?

Youre crazy, said Bibbs, obviously annoyed, since he had announced bodily incineration as his preferred method of environmentally conscious disposal from Mother Earth. Where you getting that kind of information.

A bunch of articles on the internet focus on ashes left behind and never retrieved from crematoriums. Either because the family member forgot about the loved one, didnt want to pick him or her up, or didnt have the money to pay for the fireside service. So the undertakers hold onto Johnny or Jenney for as long as possible. Then, depending upon state law, they get rid of the remains as they see fit.

Sounds harsh, said Bibbs, his face displaying concern.

Looks like our pal Bibbs might be having second thoughts about his cremation determination, said Cuffs, as he slapped his perplexed friend across the back.

Entering into the discussion, I mentioned there were other problems with the disposition of ashen remains. Containers holding loved ones often become misplaced or lost by those entrusted with their care. Urns and vases are shoved into attics, storage sheds, and old trunks, or placed onto crowded basement shelves. Like boxes filled with old unidentified photographs, over time remains are forgotten. Until discovered years later by confused descendants or clueless strangers.

Theres also the so-called convenience of cremation that affects the ritual associated with the longstanding visitation process, Cuffs said.

Acknowledging the confusion apparent on the faces of the rest of the group, he added, My recent cemetery visits involved preparation for the trip, or journey. Locating the familiar resting place. Saying a few prayers, and having a brief conversation. Finally, placing a flag, special memento, or flowers near the marble marker.

That ritual, or process, is lost when the loved one is kept in a box on the bottom detergent shelf of a laundry room.

Youre exaggerating, challenged Bibbs, becoming more annoyed as the conversation continued.

Not so, I interjected. Over time, boxed or vased remains are treated with less reverence than a traditional burial site. I recall an unusual incident, when I was interviewing a couple of quirky historians in their home. As we sat down to talk, the wife brought out four fancy urns which held the remains of both sets of parents. She set them down on the coffee table, saying she thought her deceased relatives might enjoy listening to the interview.

Shaking his head, Bibbs said, Youre making that up. No way that ever happened.

Raising my right hand, I said, I swear on the remains of my late father that have been pressed into this diamond, worn on my right hand that I did not make up the statement about that interview.

What about the story of the diamond ring? Cuffs asked, as confused as the others by my addition of that little tidbit.

Smiling, I replied, Now thats a total fabrication, I said.

Picking up on my clever reply, Jimmy asked, So your ring or the wacky story is a fabrication from cremated ashes?

Ill let you decide, placing my hand on the table, and adding, By the way, theyre called cremation crystals, or cremations diamonds. A wearable trend thats increasing in popularity, environmentally friendly and, of course, politically correct.

Shaking his head, Jimmy said, What will they think of next?

Responding, Cuffs said, We havent even touched on cryonics deep freezing you after death. Only costs about $200,000, and you might end up in the same warehouse as Walt Disney.

I think we should put that topic on the shelf for another time, I said.

Yeah! Cuffs said, right next to Bibbs ashes.

Unless his relatives toss him out in an old outhouse, added Jimmy.

Or a yard sale, I said.

After the laughter subsided, Bibbs asked, If I donate myself to science, do I have to buy a new suit?

Nope, Cuffs said. Its even cheaper than cremation, and theyll take you just the way you are.

Count me in, Bibbs said.

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Off the Cuffs: Bibbs considers donation, cremation, cryonics - Cecil Whig

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The Falcon 9 rocket is raised at launch pad 39A early Saturday for a second launch attempt. Credit: Spaceflight Now

A Falcon 9 rocket is again standing upright on launch pad 39A at NASAs Kennedy Space Center in Florida after ground teams lowered the booster Friday to swap out mice heading to the International Space Station for medical experiments.

Liftoff is set for 5:07 p.m. EDT (2107 GMT) to begin a nearly two-day journey to the space station, where the Dragon supply ship fixed to the top of the Falcon 9 rocket will arrive Monday.

The Dragon capsule, the first cargo craft SpaceX has refurbished and reused after a previous flight, is carrying nearly 6,000 pounds of experiments and equipment, including 40 mice inside specially-designed transporters for an investigation into a treatment that could combat bone loss in astronauts on long-duration space missions and osteoporosis in patients on the ground.

Once the mice arrive at the space station, astronauts will treat the rodents with NELL-1, a therapeutic treatment designed to promote bone growth, according to Chia Soo, the chief scientist for the experiment and a professor of plastic, reconstructive and orthopaedic surgery at UCLA.

Men and women past the age of 50, on the average, lose about a half-percent of bone mass per year, Soo said. But in microgravity conditions, the astronaut, on average, loses anywhere from 1 to 2 percent of bone mass per month.

She added that bone loss in astronauts has tremendous implications for humans with respect to long-term space travel or space habitation in microgravity because we end up progressively losing bone mass.

Twenty of the mice will return to Earth alive with the SpaceX Dragon supply ship in early July, the first time the commercial spacecraft has landed with live animals on-board. The 20 mice that come back alive will go to UCLAs laboratories for additional research and treatment.

The other 20 mice will remain on the space station for more observation and comparative studies with the mice on Earth. All of the animals will eventually be euthanized.

If successful, this will have tremendous implications for patients on Earth because if you look at statistics approximately one in every two to three females over the age of 50, or one in every four to five males over the age of 50, will have an osteoporosis-related fracture, Soo said.

We are hoping this study will give us some insights on how NELL-1 can work under these extreme conditions and if it can work for treating microgravity-related bone loss, which is a very accelerated, severe form of bone loss, then perhaps it can (be used) for patients one day on Earth who have bone loss due to trauma or due to aging or disease, Soo said.

After the Falcon 9 launch attempts scrub Thursday, teams lowered the launcher at pad 39A and installed a temporary white room on the Dragon capsules hatch to change out the rodent habitats and several other experiments.

The logistics are complicated, as you might imagine,Louis Stodieck, director of BioServe Space Technologies at the University of Colorado Boulder, wrote in an email to Spaceflight Now. We would normally be okay for two back-to-back launch attempts, but because orbital mechanics would not permit a launch attempt (Friday), the first scrub was automatically done for 48 hours rather than 24.

This forced us to reload with new animals and new Transporters (spaceflight habitats for the ride to space for the mice), Stodieck wrote. We plan for additional groups of mice just for such contingencies.

NASA spokesperson Dan Huot said other experiments that required a changeout for the two-day launch delay included a swarm of fruit flies launching to the space station to examine how prolonged spaceflight affects their heart function.

The hearts of the insects beat at about same rate as the human heart, making it a useful analog, scientists said.

We were back in the lab the night of the scrub setting up new egg collections and adult fly vials, said Karen Ocorr, a co-investigator on the fruit fly experiment from theSanford Burnham Research Institute. These replaced the original set of vials and have now been loaded onto the Dragon for todays attempt.

Researchers are sending between 4,000 and 6,000 fruit fly eggs to the space station, where they will hatch before coming back to Earth aboard the Dragon spacecraft.

We would like to understand the role of microgravity on astronaut heart function in order to try to prevent long-term effects when they are in space for long periods and after they come back, Ocorr said.

But there are real-world implications as well for people who are spending long periods of time in bedrest or immobilized, Ocorr said. We expect that what we find in our studies on the ISS will have implications for maintaining cardiac function in those sorts of situations.

Huot said two crystal growth expeiments and a payload to study how microgravity affects cardiac stem cells also needed to be replaced with the two-day launch delay.

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Follow Stephen Clark on Twitter: @StephenClark1.

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[ June 3, 2017 ] SpaceX rocket again set for station delivery after scientists swap mice, fruit flies Mission Reports - Spaceflight Now

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COUNTLESS lives across the world could be saved by an Oxfordshire familys appeal to find a bone marrow donor for their little boy.

Two-year-old Alastair Ally Kim has Chronic Granulomatous Disorder (CGD), a life-threatening condition.

He has now become the fourth person in the world to start an experimental gene therapy course at Great Ormond Street Hospital.

In the meantime, his parents have spearheaded 200 international donor drives to find their son a match, signing up 7,000 would-be donors in the process - some of whom have since been matched with other patients.

Father Andrew Kim, 37, of Hinton Waldrist near Longworth, said: We want to use whatever momentum Allys story has to help someone else. We know that matches have come through our drives for other people. Its awesome that someone will benefit from all this.

On Thursday, May 25 family friend Cathy Oliveira organised a drive at the Oxford Universitys Old Road research building, signing up 80 staff members in a day.

Ms Oliveira said: When everything happened with Ally I wanted to show support in any way we could; this is directly beneficial not just for Ally but for others.

Allys CGD means his immune system is compromised and the tiniest infection could leave him seriously ill.

His only chance of a permanent cure is a bone marrow stem cell donation, with a match likely to be of Korean or East Asian origin.

In April the youngster and mum Judy Kim, 36, an Oxford University researcher, travelled to London for him to begin a pioneering new gene therapy treatment.

After a week of chemotherapy to wipe out Allys immune system, cells taken from him are modified in a lab and re-introduced to correct the disorder.

Mr Kim said: Bone marrow would give him back 100 per cent functionality and gene therapy is 10 to 15 per cent; its enough to live in the real world, and not be scared he will die every time he gets an infection.

It has been a roller-coaster of a year, but theres nothing to do but move forward. We are really excited at the thought of him being able to come home this summer.

Blood cancer charity DKMS supported last weeks donor drive in Oxford.

Senior donor recruitment manager Joe Hallet said: Around 30 per cent of patients in need of a blood stem cell donor will find a matching donor within their own family.

The remaining 70 per cent, like Ally, will need to find an unrelated donor to have a second chance of life, so events like these are crucial.

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Oxford University staff join bone marrow stem cell donor drive for Oxford toddler Ally Kim - Witney Gazette

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Miami Herald

Want to save a life? Cuban American searches for bone marrow donor Miami Herald According to Gift of Life, a nonprofit, Boca Raton-based bone marrow and blood stem cell registry, 55 percent of Hispanic cancer patients and 75 percent of multiracial patients are never matched, some dying while waiting to get a transplant. The data ...

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Want to save a life? Cuban American searches for bone marrow donor - Miami Herald

Recommendation and review posted by Bethany Smith

(CNN) Here is some background information about stem cells.

Scientists believe that stem cell research can be used to treat medical conditions including Parkinsons disease, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis and rheumatoid arthritis.

About Stem Cells:Stem cell research focuses on embryonic stem cells and adult stem cells.

Stem cells have two characteristics that differentiate them from other types of cells:- Stem cells are unspecialized cells that replicate themselves for long periods through cell division.- Under certain physiologic or experimental conditions, stem cells can be induced to become mature cells with special functions such as the beating cells of the heart muscle or insulin-producing cells of the pancreas.

There are four classes of stem cells: totipotent, multipotent, pluripotent, and unipotent.- Totipotent stem cells that develop into cells that make up all the cells in an embryo and fetus. (Ex: The zygote/fertilized egg and the cells at the very early stages following fertilization are considered totipotent)- Multipotent stem cells can give rise to multiple types of cells, but all within a particular tissue, organ, or physiological system. (Ex: blood-forming stem cells/bone marrow cells, most often referred to as adult stem cells)- Pluripotent stem cells (ex: embryonic stem cells) can give rise to any type of cell in the body. These cells are like blank slates, and they have the potential to turn into any type of cell.- Unipotent stem cells can self-renew as well as give rise to a single mature cell type. (Ex: sperm producing cells)

Embryonic stem cells are harvested from four to six-day-old embryos. These embryos are either leftover embryos in fertility clinics or embryos created specifically for harvesting stem cells by therapeutic cloning. Only South Korean scientists claim to have successfully created human embryos via therapeutic cloning and have harvested stem cells from them.

Adult stem cells are already designated for a certain organ or tissue. Some adult stem cells can be coaxed into or be reprogrammed into turning into a different type of specialized cell within the tissue type for example, a heart stem cell can give rise to a functional heart muscle cell, but it is still unclear whether they can give rise to all different cell types of the body.

The primary role of adult stem cells is to maintain and repair the tissue in which they are found.

Uses of Stem Cell Research:Regenerative (reparative) medicine uses cell-based therapies to treat disease.

Scientists who research stem cells are trying to identify how undifferentiated stem cells become differentiated as serious medical conditions, such as cancer and birth defects, are due to abnormal cell division and differentiation.

Scientists believe stem cells can be used to generate cells and tissues that could be used for cell-based therapies as the need for donated organs and tissues outweighs the supply.

Stem cells, directed to differentiate into specific cell types, offer the possibility of a renewable source of replacement cells and tissues to treat diseases, including Parkinsons and Alzheimers diseases, spinal cord injury, stroke, burns, heart disease, diabetes, osteoarthritis, and rheumatoid arthritis.

Policy Debate:Cloning human embryos for stem cells is very controversial.

The goal of therapeutic cloning research is not to make babies, but to make embryonic stem cells, which can be harvested and used for cell-based therapies.

Using fertilized eggs left over at fertility clinics is also controversial because removing the stem cells destroys them.

Questions of ethics arise because embryos are destroyed as the cells are extracted, such as: When does human life begin? What is the moral status of the human embryo?

Timeline:1998 President Bill Clinton requests a National Bioethics Advisory Commission to study the question of stem cell research.

1999 The National Bioethics Advisory Commission recommends that the government allow federal funds to be used to support research on human embryonic stem cells.

2000 During his campaign, George W. Bush says he opposes any research that involves the destruction of embryos.

2000 The National Institutes of Health (NIH) issues guidelines for the use of embryonic stem cells in research, specifying that scientists receiving federal funds can use only extra embryos that would otherwise be discarded. President Clinton approves federal funding for stem cell research but Congress does not fund it.

August 9, 2001 President Bush announces he will allow federal funding for about 60 existing stem cell lines created before this date.

January 18, 2002 A panel of experts at the National Academy of Sciences (NAS) recommends a complete ban on human reproductive cloning, but supports so-called therapeutic cloning for medical purposes.

February 27, 2002 For the second time in two years, the House passes a ban on all cloning of human embryos.

July 11, 2002 The Presidents Council on Bioethics recommends a four-year ban on cloning for medical research to allow time for debate.

February 2005 South Korean scientist Hwang Woo Suk publishes a study in Science announcing he has successfully created stem cell lines using therapeutic cloning.

December 2005 Experts from Seoul National University Hwang of faking some of his research. Hwang asks to have his paper withdrawn while his work is being investigated and resigns his post.

January 10, 2006 An investigative panel from Seoul National University accuses Hwang of faking his research.

July 18, 2006 The Senate votes 63-37 to loosen President Bushs limits on federal funding for embryonic stem-cell research.

July 19, 2006 President Bush vetoes the embryonic stem-cell research bill passed by the Senate (the Stem Cell Research Enhancement Act of 2005), his first veto since taking office.

June 20, 2007 President Bush vetoes the Stem Cell Research Enhancement Act of 2007, his third veto of his presidency.

January 23, 2009 The FDA approves a request from Geron Corp. to test embryonic stem cells on eight to 10 patients with severe spinal cord injuries. This will be the worlds first test in humans of a therapy derived from human embryonic stem cells. The tests will use stem cells cultured from embryos left over in fertility clinics.

March 9, 2009 President Barack Obama signs an executive order overturning an order signed by President Bush in August 2001 that barred the NIH from funding research on embryonic stem cells beyond using 60 cell lines that existed at that time.

August 23, 2010 US District Judge Royce C. Lamberth issues a preliminary injunction that prohibits the federal funding of embryonic stem cell research.

September 9, 2010 A three-judge panel of the US Court of Appeals for the D.C. Circuit grants a request from the Justice Department to lift a temporary injunction that blocked federal funding of stem cell research.

September 28, 2010 The US Court of Appeals for the District of Columbia Circuit lifts an injunction imposed by a federal judge, thereby allowing federally funded embryonic stem-cell research to continue while the Obama Administration appeals the judges original ruling against use of public funds in such research.

October 8, 2010 The first human is injected with cells from human embryonic stem cells in a clinical trial sponsored by Geron Corp.

November 22, 2010 William Caldwell, CEO of Advanced Cell Technology, tells CNN that the FDA has granted approval for his company to start a clinical trial using cells grown from human embryonic stem cells. The treatment will be for an inherited degenerative eye disease.

April 29, 2011 The US Court of Appeals for the District of Columbia lifts an injunction, imposed last year by a federal judge, banning the Obama administration from funding embryonic stem-cell research.

May 11, 2011 Stem cell therapy in sports medicine is spotlighted after New York Yankee pitcher Bartolo Colon is revealed to have had fat and bone marrow stem cells injected into his injured elbow and shoulder while in the Dominican Republic.

July 27, 2011 Judge Lamberth dismisses a lawsuit that tried to block funding of stem cell research on human embryos.

February 13, 2012 Early research published by scientists at Cedars-Sinai Medical Center and Johns Hopkins University show that a patients own stem cells can be used to regenerate heart tissue and help undo damage caused by a heart attack. It is the first instance of therapeutic regeneration.

May 2013 Scientists make the first embryonic stem cell from human skin cells by reprogramming human skin cells back to their embryonic state, according to a study published in the journal, Cell.

April 2014 For the first time scientists are able to use cloning technologies to generate stem cells that are genetically matched to adult patients,according to a study published in the journal, Cell Stem Cell.

October 2014 Researchers say that human embryonic stem cells have restored the sight of several nearly blind patients and that their latest study shows the cells are safe to use long-term. According to a report published in The Lancet, the researchers transplanted stem cells into 18 patients with severe vision loss as a result of two types of macular degeneration.

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A new research paper is stirring up controversy among scientists interested in using DNA editing to treat disease.

In a two-page article published in the journal Nature Methods on May 30, a group of six scientists report an alarming number of so-called off-target mutations in mice that underwent an experimental gene repair therapy.

CRISPR, the hot new gene-editing technique thats taken biology by storm, is no stranger to headlines. What is unusual, however, is a scientific article so clearly describing a potentially fatal shortcoming of this promising technology.

The research community is digesting this news with many experts suggesting flaws with the experiment, not the revolutionary technique.

Unwanted DNA changes

The research team sought to repair a genetic mutation known to cause a form of blindness in mice. This could be accomplished, they showed, by changing just one DNA letter in the mouse genome.

They were able to successfully correct the targeted mutation in each of the two mice they treated. But they also observed an alarming number of additional DNA changes more than 1,600 per mouse in areas of the genome they did not intend to modify.

The authors attribute these unintended mutations to the experimental CRISPR-based gene editing therapy they used.

A central promise of CRISPR-based gene editing is its ability to pinpoint particular genes. But if this technology produces dangerous side effects by creating unexpected and unwanted mutations across the genome, that could hamper or even derail many of its applications.

Several previous research articles have reported off-target effects of CRISPR, but far fewer than this group found.

Reaction is skeptical

The publicly traded biotech companies seeking to commercialize CRISPR-based gene therapies Editas Medicine, Intellia Therapeutics and Crispr Therapeuticsall took immediate stock market hits based on the news.

Experts in the field quickly responded.

Either the enzyme is acting at near optimal efficiency or something fishy is going on here, tweeted Matthew Taliaferro, a postdoctoral fellow at MIT who studies gene expression and genetic disease. The Cas9 enzyme in the CRISPR system is what actually cuts DNA, leading to genetic changes. Unusually high levels of enzyme activity could account for the observed off-target mutations more cutting equals more chances for the cell to mutate its DNA. Different labs use slightly different methods to try to ensure the right amount of cuts happen only where intended.

Unusual methods were used, tweeted Lluis Montoliu, who runs a lab at the Spanish National Centre for Biotechnology that specializes in editing mice genes using CRISPR. He believes the authors used suboptimal molecular components in their injected CRISPR therapies specifically a plasmid that causes cells to produce too much Cas9 enzyme likely leading to the off-target effects they observed.

Gatan Burgio, whose laboratory at the Australian National University is working to understand the role that cellular context plays on CRISPR efficiency, believes the papers central claim that CRISPR caused such an alarming number of off-target mutations is not substantiated.

Burgio says there could be a range of reasons for seeing so many unexpected changes in the mice, including problems with accurately detecting DNA variation, the extremely small number of mice used, random events happening after Cas9 acted or, he concedes, problems with CRISPR itself.

Burgio has been editing the DNA of mice using CRISPR since 2014 and has never seen a comparable level of off-target mutation. He says hes confident that additional research will refute these recent findings.

Continuing CRISPR work

Although the news of this two-mouse experiment fired up the science-focused parts of the Twittersphere, the issue it raises is not new to the field.

Researchers have known for a few years now that off-target mutations are likely given certain CRISPR protocols. More precise variants of the Cas9 enzyme have been shown to improve targeting in human tissue the lab.

Researchers have also focused on developing methods to more efficiently locate off-target mutations in the animals they study.

As scientists continue to hone the gene-editing technique, we recognize theres still a way to go before CRISPR will be ready for safe and effective gene therapy in humans.

Ian Haydon, Doctoral Student in Biochemistry, University of Washington

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CRISPR controversy raises questions about gene-editing technique ... - Salon

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Scientists have used gene therapy to 'switch off' the immune response that causes asthma, and are hopeful that the same technique could be used to target other severe allergies to peanuts, bee venom, and shellfish,keeping them at bay for life.

The research, which has so far seen success in animal trials, works byerasing the memory of the cells responsible for causing an allergic reaction, and if replicated in humans, could offer a one-off treatment for allergy patients.

"The challenge in asthma and allergies is that these immune cells, known as T-cells, develop a form of immune 'memory', and become very resistant to treatments,"says lead researcherRay Steptoefrom the University of Queensland (UQ) in Australia.

"We have now been able 'wipe' the memory of these T-cells in animals with gene therapy, de-sensitising the immune system so that it tolerates the [allergen] protein."

An allergic response is a hypersensitive immune reaction to a substance that is normally harmless. When people are exposed to their allergic trigger, it can cause anything from itchy eyes and a runny nose to - in the most extreme cases -death.

Asthma is a common allergic response of the airways affecting 2.5 million Australiansand hundreds of millions around the world. About 80 percent of people who experience asthma in Australia are susceptible to hay fever - an allergic response to rye grass pollen.

"When someone has an allergy or asthma flare-up, the symptoms they experience results from immune cells reacting to protein in the allergen," says lead researcherRay Steptoefrom the University of Queensland (UQ) in Australia.

While previous research has looked into using nanoparticle 'trojan horses' to smuggle the allergen past the immune system, and at new immunotherapy approaches, right now, the most effective treatment for people suffering from allergies is to simply avoid all known triggers.

To figure out a better way, Steptoe and his teamtook bone marrow from mice that had been genetically modified to have a resistance against asthma caused by rye grass pollen, and transplanted the bone marrow into unmodified mice.

"We take blood stem cells, insert a gene which regulates the allergen protein, and we put that into the recipient," says Steptoe.

"Those engineered cells produce new blood cells programmed to express the protein and target specific immune cells, which 'turn off' the allergic response."

Even though this study only looked at asthma, the researchers hope that the same approach could be used to provide protection against other common allergies - food and otherwise.

"Our work used an experimental asthma allergen, but this research could be applied to treat those who have severe allergies to peanuts, bee venom, shellfish and the like," Steptoe said.

But before we start throwing our puffers in the bin, the studies still have to be replicated in human trials, and that's where things get much more complicated.

"In the real world, unfortunately, it's not just usually a single allergen protein [that causes an immune response]. There might be several proteins that you might be allergic to and you'd have to target each of those proteins," Steptoe told ScienceAlert.

"We're currently doing experiments to see if we can turn off multiple response at the same time."

The research is published in JCI Insight.

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Gene therapy has been used to 'switch off' asthma symptoms - ScienceAlert

Recommendation and review posted by Bethany Smith

Posted June 03, 2017 08:59:49

Sufferers of severe allergies like asthma and lethal food allergies could gain lifetime relief in a single treatment, according to scientists at the University of Queensland.

The researchers believe a simple injection that will "turn off" the immune response that causes allergic reactions in affected people could be available within 10 years.

Immunologist Associate Professor Ray Steptoe said it was a "major breakthrough".

"Learning how to turn off this immune response has been challenge for immunotherapy for a long time," Dr Steptoe said.

"We haven't quite got it to the point where it's as simple as getting a flu jab, so we are working on making it simpler and safer so it could be used across a wide cross-section of affected individuals."

Dr Steptoe said allergic symptoms, such as breathing difficulties, occur when immune cells known as T-cells react to the protein in allergens.

"The challenge is that these T-cells develop a form of immune 'memory' and become very resistant to treatments," he said.

The researchers worked with an asthma allergen and used gene therapy to break the damaging cycle.

"We have now been able 'wipe' the memory of these T-cells in animals with gene therapy, de-sensitising the immune system so that it tolerates the protein," Dr Steptoe said.

"The research could be applied treat those who have severe allergies to peanuts, bee venom, shell fish and the like."

Importantly, the therapy specifically targets the memory for the allergen protein, while leaving other immune responses unaffected.

"It does it in a highly targeted way, without turning off the memory that is protective such as the important immune response you get from vaccinations, the ones that protect you from the flu and other infectious diseases we're vaccinated against," he said.

The research findings have been welcomed by the Asthma Foundation of Queensland and New South Wales, which said it looked forward to the development of future treatments.

CEO Dr Peter Anderson said more than one million Australians suffered with asthma symptoms.

"The Foundation welcomes the findings of this research and looks forward to a day in the future when a safe one-off treatment may be available that has the potential to eliminate any experience of asthma in vulnerable patients," he said.

Topics: health, diseases-and-disorders, allergies, medical-research, qld, brisbane-4000

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Allergy research 'breakthrough' could lead to treatment in a decade ... - ABC Online

Recommendation and review posted by Bethany Smith

Contributor: Jame Abraham, MD

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Its not unusual for a patient to ask if men can get breast cancer, and the answer to the question is yes. In 2017, about 2,470 new cases of invasive breast cancer will be diagnosed, and about 460 men will die from breast cancer, according to the American Cancer Society.

But breast cancer is about 100 times less common among men than among women. For men, the lifetime risk of getting breast cancer is about 1 in 1,000. The number of breast cancer cases in males relative to the population has been fairly stable over the last 30 years.

The most common symptoms of male breast cancer are:

There are myriad risk factors that increase the odds of a man developing breast cancer, but many men will develop the disease without experiencing any of these. Many risk factors are similar for men and women, including age, family history and genetic mutations.

One risk factor that increases the risk of breast cancer for both men and women is aging. In general, the risk of breast cancer goes up as a man ages, with an average age of diagnosis of 68.

Family history is important, too, as breast cancer risk is higher if other members of the family have had the disease. About 20 percent of men with breast cancer have a family history of it.

Genetic mutations, such as the BRCA2 gene, increase the risk of breast cancer for anyone, with a lifetime risk of 6 in 100. BRCA1 mutations, in particular, can increase the risk for breast cancer in men; the risk is about 1 in 100. Other important mutations are the CHEK2 and PTEN genes, which may be responsible for some breast cancers in men.

Theres a congenital condition called Klinefelter syndrome that affects 1 in 1,000 men. In normal men, the cells have a single X chromosome with a Y chromosome, while womens cells have two X chromosomes. Men with Klinfelter syndrome have cells with a Y chromosome, plus at least two X chromosomes. These men also have smaller-than-usual testicles, and theyre often infertile because theyre unable to produce functioning sperm cells. Compared with other men, they have lower levels of the male hormone androgen and more of the famale hormone estrogen. For this reason, they often develop swelling of the breast tissue, called gynecomastia. Some studies have shown that among men with this syndrome, the risk of getting breast cancer was about 1 percent, or 1 in 100.

Having been exposed to radiation in the past is also a risk factor for breast cancer in men. A man who had radiation to the chest for lymphoma or any other conditions has an increased risk of developing breast cancer.

Heavy alcohol consumption and liver disease increase the risk of breast cancer in men. Other risk factors include estrogen therapy or other hormonal therapy for prostate cancer, obesity, testicular condition such as undescended testis and some occupations, such as steel mill workers.

In general, the way male breast cancer is managed is similar to tactics used with female breast cancer. The disease could be diagnosed via a clinical examination, mammogram or ultrasound and, if an abnormality is found, the man will be considered for a biopsy of the lesion.

Definite treatment will include surgerythat may include removal of the breast, lump and lymph node surgery, and possibly chemotherapy and anti-estrogen therapy.

Overall prognosis depends upon the stage and other features of breast cancer.

Male breast cancer survivors face many challenges, since its a rare condition. Most of the data related to male breast cancer is derived from female breast cancer. We have only very limited data about specific treatment, prognosis and outcome of male breast cancer.

Its important for men with breast cancer to take care of themselves. This includes being compliant with their cancer treatment and having appropriate follow up.

Adopting a healthy lifestyle that includes eating healthy, exercising and avoiding tobacco and alcohol is imperative. Its a good idea to look for clinical trials; unfortunately, however, many breast cancer trials exclude men. My hope for patients is that this will change in the future.

This post is based on one of a series of articles produced by U.S. News & World Report in association with the medical experts at Cleveland Clinic.

More:
Male Breast Cancer: Less Common Than For Women, But Still Serious - Health Essentials from Cleveland Clinic (blog)

Recommendation and review posted by Bethany Smith

Thursday, June 01, 2017 11:40 a.m. CDT

By Lisa Rapaport

(Reuters Health) - Women who dont have access to reproductive health clinics can safely use telemedicine services to consult with a doctor and get drugs to terminate their pregnancy without surgery, suggests a study of Irish women.

About one quarter of the worlds population lives in countries with highly restrictive abortion laws and where women may resort to unsafe methods to end pregnancies. This results in an estimated 43,000 deaths every year, researchers write in The BMJ.

The current study focused on 1,000 women who used an online telemedicine service to get medical abortions in the Republic of Ireland and Northern Ireland, where abortions are illegal in most circumstances.

About 95 percent of the women reported successfully terminating their pregnancies without surgical intervention using medication they received in the mail after providing their medical details and consulting with a trained helpdesk team on how to use the drug. No deaths were reported, and less than 3 percent of the women had complications that required treatment like antibiotics or blood transfusions.

The results provide the best evidence to date that medication abortion conducted entirely outside the formal healthcare setting using online telemedicine can be highly effective and safe, said lead study author Dr. Abigail Aiken, a researcher at the University of Texas at Austin.

All of the women in the study got abortion pills through Women on Web (WoW), a nonprofit organization that provides access to medical abortions early in pregnancy for women who live in countries where access to safe abortion is limited.

While Women on Web only provides medication abortion through online telemedicine in countries where abortion is restricted, the findings of our study suggest that this model may be much more widely applicable, Aiken said by email. As long as a woman does not have a contraindication to medication abortion (there are a few of these, but they are rare) and her pregnancy is at a gestational age appropriate for the approved use of the medications in her country, medication abortion using a reputable online telemedicine service may be an appropriate option if she needs or prefers it.

Surgical abortions require in-person clinic visits, but many abortions are now done with medication and a growing number of women are getting pills by consulting with doctors online even when they live in places where abortion is legal.

In the U.S., medication abortions are typically performed before 10 weeks of pregnancy with two drugs mifepristone and misoprostol that can be self-administered at home. Healthcare providers can use telemedicine to interview patients and assess potential safety issues by reviewing lab test results and ultrasounds before prescribing medication.

In a typical two-step medical abortion regimen, women first take mifepristone. This pill works by blocking the hormone progesterone, which causes the lining of the uterus to break down and makes it impossible for the pregnancy to continue. Then, a day or two later, women take misoprostol, which causes the uterus to empty.

Women may be advised to have a clinic visit afterwards to confirm that the pregnancy was successfully terminated. In rare cases when ultrasound or a blood test shows the medical abortion didnt succeed, women require surgical abortions.

In the study, 93 women, or about 9 percent, experienced a symptom that they were told required medical attention, and most of the women followed advice to visit a clinician in person.

One limitation of the study is its reliance on women to accurately recall and report any side effects or problems, the authors note.

Still, women should be reassured by the results, said Dr. Wendy Norman, a researcher at the University of British Columbia in Vancouver who co-wrote an accompanying editorial.

When a woman has access to see a clinician in person to obtain a medical abortion, that is the preferred method, Norman told Reuters Health by email. In areas where medical abortion providers are not available, or areas where abortion is legally restricted, access to a qualified clinician via telemedicine provides a reasonable alternative to discuss the current pregnancy in the context of a woman's general health and health history, consider available options for her pregnancy, and to provide management of a medical abortion from start to finish if desired.

SOURCE: http://bit.ly/2rY2FQL and http://bit.ly/2qEP9xs The BMJ, online May 16, 2017.

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Online access to abortion pill may be safe alternative to clinics - KFGO

Recommendation and review posted by simmons

Editors note: The SpaceX Falcon 9 rocket scheduled to launch today from Florida was delayed due to weather conditions. The launch has been rescheduled for Saturday, June 3.

A SpaceX rocket wasslated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida on Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida, and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

Continue reading here:
SpaceX to launch CU-built heart, bone health experiments to space station - CU Boulder Today

Recommendation and review posted by simmons

Vistagen Therapeutics, Inc.

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"VistaGen Therapeutics, Inc. (NASDAQ: VTGN), is a clinical-stage biopharmaceutical company focused on developing new generation medicines for depression and other central nervous system (CNS) disorders. Our lead CNS product candidate, AV-101, is a new generation oral antidepressant drug candidate in Phase 2 development. AV-101's mechanism of action is fundamentally differentiated from all FDA-approved antidepressants and atypical antipsychotics used adjunctively to treat major depressive disorder (MDD), with potential to drive a paradigm shift towards a new generation of safer and faster-acting antidepressants. AV-101 is currently being evaluated by the U.S. National Institute of Mental Health (NIMH) in a Phase 2 monotherapy study in MDD being fully funded by the NIMH and conducted by Dr. Carlos Zarate Jr., Chief, Section on the Neurobiology and Treatment of Mood Disorders and Chief of Experimental Therapeutics and Pathophysiology Branch at the NIMH, and one of the world's foremost experts on the use of low dose IV ketamine and other NMDA receptor antagonists to treat MDD. VistaGen is also preparing to launch a 180-patient Phase 2 study of AV-101 as an adjunctive treatment for MDD patients with inadequate response to standard, FDA-approved antidepressant therapies. Dr. Maurizio Fava of Harvard University will be the Principal Investigator of the Phase 2 adjunctive treatment study. AV-101 may also have the potential to treat multiple CNS disorders and neurodegenerative diseases in addition to MDD, including chronic neuropathic pain, epilepsy, Parkinson's disease and Huntington's disease, where modulation of the NMDAR, AMPA pathway and/or key active metabolites of AV-101 may achieve therapeutic benefit. In addition to our AV-101 programs, VistaStem, VistaGens wholly owned subsidiary, is applying our human pluripotent stem cell (hPSC) technology platform and CardioSafe 3D, our customized in-vitro human cardiac cell bioassay system, to predict potential heart toxicity of new chemical entities (NCEs) long before they are tested in preclinical animal studies and human clinical studies. Having successfully assessed AV-101 and numerous other drug candidates to establish the clinically predictive capabilities of CardioSafe 3D, we are now using CardioSafe 3D to expand our pipeline through cardiac liability-focused small molecule drug rescue, and to participate, together with a select group of companies, in the FDA's Comprehensive in-vitro Proarrhythmia Assay (CIPA) initiative designed to change the landscape of preclinical drug development by providing a more complete and accurate assessment of potential drug effects on cardiac risk. We are also focused on collaborating with others to advance development and commercialization of medicine and cell therapy applications of our stem cell technology across a range of cell types, including blood, bone, cartilage, heart and liver cells. In December 2016, we entered into an exclusive sublicense agreement with BlueRock Therapeutics L.P, a next generation regenerative medicine company established by Bayer AG and Versant Ventures, for our rights to proprietary technologies relating to the production of cardiac stem cells for the treatment of heart disease."

Read more:
Vistagen Therapeutics, Inc. - Seeking Alpha

Recommendation and review posted by sam

Editors note: The SpaceX Falcon 9 rocket scheduled to launch today from Florida was delayed due to weather conditions. The launch has been rescheduled for Saturday, June 3.

A SpaceX rocket wasslated to launch two University of Colorado Boulder-built payloads to the International Space Station (ISS) from Florida on Thursday, including oneto look at changes in cardiovascular stem cells in microgravity that may someday help combat heart disease on Earth.

The Dragon spacecraft

The second payload will be used for rodent studies testing a novel treatment for bone loss in space, which has been documented in both astronauts and mice. The two payloads were developed by BioServe Space Technologies, a research center within the Ann and H.J Smead Department of Aerospace Engineering,

We have a solid relationship with SpaceX and NASA that allows us to regularly fly our flight hardware to the International Space Station, said BioServe Director Louis Stodieck. The low gravity of space provides a unique environment for biomedical experiments that cannot be reproduced on Earth, and our faculty, staff and students are very experienced in designing and building custom payloads for our academic, commercial and government partners.

The experiments will be launched on a SpaceX Falcon 9 rocket from Cape Canaveral, Florida, and carried to the ISS on the companys Dragon spacecraft. The SpaceX-CRS-11 mission launching Thursday marks BioServes 55th mission to space.

The cardiovascular cell experiments, designed by Associate Professor Mary Kearns-Jonker of the Loma Linda University School of Medicine in Loma Linda, California, will investigate how low gravity affects stem cells, including physical and molecular changes. While spaceflight is known to affect cardiac cell structure and function, the biological basis for such impacts is not clearly understood, said BioServe Associate director Stefanie Countryman.

As part of the study, the researchers will be comparing changes in heart muscle stem cells in space with similar cells simultaneously cultured on Earth, said Countryman. Researchers are hopeful the findings could help lead to stem cell therapies to repair damaged cardiac tissue. The findings also could confirm suspicions by scientists that microgravity speeds up the aging process, Countryman said.

For the heart cell experiments, BioServe is providing high-tech, cell-culture hardware known as BioCells that will be loaded into shoebox-sized habitats on ISS. The experiments will be housed in BioServes Space Automated Bioproduct Lab (SABL), a newly updated smart incubator that will reduce the time astronauts spend manipulating the experiments.

The second experiment, created by Dr. Chia Soo of the UCLA School of Medicine, will test a new drug designed to not only block loss of bone but also to rebuild it.

The mice will ride in a NASA habitat designed for spaceflight to the ISS. Once on board, some mice will undergo injections with the new drug while others will be given a placebo. At the end of the experiments half of the mice will be returned to Earth in SpaceXs Dragon spacecraft and transported to UCLA for further study, said Stodieck, a scientific co-investigator on the experiment.

BioServes Space Automated Byproduct Lab

In addition to the two science experiments, BioServe is launching its third SABL unit to the ISS. Two SABL units are currently onboard ISS supporting multiple research experiments, including three previous stem cell experiments conducted by BioServe in collaboration with Stanford University, the Mayo Clinic and the University of Minnesota.

The addition of the third SABL unit will expand BioServes capabilities in an era of high-volume science on board the ISS, said Countryman.

BioServe researchers and students have flown hardware and experiments on missions aboard NASA space shuttles, the ISS and on Russian and Japanese government cargo rockets. BioServe previously has flown payloads on commercial cargo rockets developed by both SpaceX, headquartered in Hawthorne, California, and Orbital ATK, Inc. headquartered in Dulles, Virginia.

Since it was founded by NASA in 1987, BioServe has partnered with more than 100 companies and performed dozens of NASA-sponsored investigations. Itspartners include large and small pharmaceutical and biotechnology companies, universities and NASA-funded researchers, and investigations sponsored by the Center for the Advancement of Science in Space, which manages the ISS U.S. National Laboratory. CU-Boulder students are involved in all aspects of BioServe research efforts, said Stodieck.

Excerpt from:
SpaceX to launch heart, bone health experiments to space station - CU Boulder Today

Recommendation and review posted by sam

COUNTLESS lives across the world could be saved by an Oxfordshire familys appeal to find a bone marrow donor for their little boy.

Two-year-old Alastair Ally Kim has Chronic Granulomatous Disorder (CGD), a life-threatening condition.

He has now become the fourth person in the world to start an experimental gene therapy course at Great Ormond Street Hospital.

In the meantime, his parents have spearheaded 200 international donor drives to find their son a match, signing up 7,000 would-be donors in the process - some of whom have since been matched with other patients.

Father Andrew Kim, 37, of Hinton Waldrist near Longworth, said: We want to use whatever momentum Allys story has to help someone else. We know that matches have come through our drives for other people. Its awesome that someone will benefit from all this.

On Thursday, May 25 family friend Cathy Oliveira organised a drive at the Oxford Universitys Old Road research building, signing up 80 staff members in a day.

Ms Oliveira said: When everything happened with Ally I wanted to show support in any way we could; this is directly beneficial not just for Ally but for others.

Allys CGD means his immune system is compromised and the tiniest infection could leave him seriously ill.

His only chance of a permanent cure is a bone marrow stem cell donation, with a match likely to be of Korean or East Asian origin.

In April the youngster and mum Judy Kim, 36, an Oxford University researcher, travelled to London for him to begin a pioneering new gene therapy treatment.

After a week of chemotherapy to wipe out Allys immune system, cells taken from him are modified in a lab and re-introduced to correct the disorder.

Mr Kim said: Bone marrow would give him back 100 per cent functionality and gene therapy is 10 to 15 per cent; its enough to live in the real world, and not be scared he will die every time he gets an infection.

It has been a roller-coaster of a year, but theres nothing to do but move forward. We are really excited at the thought of him being able to come home this summer.

Blood cancer charity DKMS supported last weeks donor drive in Oxford.

Senior donor recruitment manager Joe Hallet said: Around 30 per cent of patients in need of a blood stem cell donor will find a matching donor within their own family.

The remaining 70 per cent, like Ally, will need to find an unrelated donor to have a second chance of life, so events like these are crucial.

Original post:
Oxford University staff join bone marrow stem cell donor drive for ... - Oxford Mail

Recommendation and review posted by Bethany Smith

COUNTLESS lives across the world could be saved by an Oxfordshire familys appeal to find a bone marrow donor for their little boy.

Two-year-old Alastair Ally Kim has Chronic Granulomatous Disorder (CGD), a life-threatening condition.

He has now become the fourth person in the world to start an experimental gene therapy course at Great Ormond Street Hospital.

In the meantime, his parents have spearheaded 200 international donor drives to find their son a match, signing up 7,000 would-be donors in the process - some of whom have since been matched with other patients.

Father Andrew Kim, 37, of Hinton Waldrist near Longworth, said: We want to use whatever momentum Allys story has to help someone else. We know that matches have come through our drives for other people. Its awesome that someone will benefit from all this.

On Thursday, May 25 family friend Cathy Oliveira organised a drive at the Oxford Universitys Old Road research building, signing up 80 staff members in a day.

Ms Oliveira said: When everything happened with Ally I wanted to show support in any way we could; this is directly beneficial not just for Ally but for others.

Allys CGD means his immune system is compromised and the tiniest infection could leave him seriously ill.

His only chance of a permanent cure is a bone marrow stem cell donation, with a match likely to be of Korean or East Asian origin.

In April the youngster and mum Judy Kim, 36, an Oxford University researcher, travelled to London for him to begin a pioneering new gene therapy treatment.

After a week of chemotherapy to wipe out Allys immune system, cells taken from him are modified in a lab and re-introduced to correct the disorder.

Mr Kim said: Bone marrow would give him back 100 per cent functionality and gene therapy is 10 to 15 per cent; its enough to live in the real world, and not be scared he will die every time he gets an infection.

It has been a roller-coaster of a year, but theres nothing to do but move forward. We are really excited at the thought of him being able to come home this summer.

Blood cancer charity DKMS supported last weeks donor drive in Oxford.

Senior donor recruitment manager Joe Hallet said: Around 30 per cent of patients in need of a blood stem cell donor will find a matching donor within their own family.

The remaining 70 per cent, like Ally, will need to find an unrelated donor to have a second chance of life, so events like these are crucial.

Read more:
Donor appeal for poorly toddler 'may have saved other lives' - Witney Gazette

Recommendation and review posted by simmons

Blood stem cells are things of wonder: hidden inside each single cell is the power to reconstitute an entire blood system, like a sort of biological big bang.

Yet with great power comes greater vulnerability. Once these master cells are compromised, as in the case of leukemia and other blood disorders, treatment options are severely limited.

A bone marrow transplant is often the only chance for survival. The surgery takes a healthy donors marrowrich with blood stem cellsand reboots the patients blood system. Unfortunately, like organ transplants, finding a matching donor places a chokehold on the entire process.

According to Dr. George Daley at Harvard Medical School, a healthy sibling gives you a one in four chance. A stranger? One in a million.

For 20 years, scientists have been trying to find a way to beat the odds. Now, two studies published in Nature suggest they may be tantalizingly close to being able to make a limitless supply of blood stem cells, using the patients own healthy tissues.

"This step opens up an opportunity to take cells from patients with genetic blood disorders, use gene editing to correct their genetic defect and make functional blood cells," without depending on donors, says Dr. Ryohichi Sugimura at Boston Childrens Hospital, who authored one of the studies with Daley.

Using a magical mix of seven proteins called transcription factors, the team coaxed lab-made human stem cells into primordial blood cells that replenished themselves and all components of blood.

A second study led by Dr. Shahin Rafii, a stem cell scientist at Weill Cornell Medical College took a more direct route, turning mature cells from mice straight into genuine blood stem cells indiscernible from their natural counterparts.

This is the first time researchers have checked all the boxes and made blood stem cells, says Dr. Mick Bhatia at McMaster University, who was not involved in either study, That is the holy grail.

The life of a blood stem cell starts as a special cell nestled on the walls of a large blood vesselthe dorsal aorta.

Under the guidance of chemical signals, these cells metamorphose into immature baby blood stem cells, like caterpillars transforming into butterflies. The exact conditions that prompt this birthing process are still unclear and is one of the reasons why lab-grown blood stem cells have been so hard to make.

These baby blood stem cells dont yet have the full capacity to reboot blood systems. To fully mature, they have to learn to respond to all sorts of commands in their environment, like toddlers making sense of the world.

Some scientists liken this learning process to going to school, where different external cues act as textbooks to train baby blood stem cells to correctly respond to the body.

For example, when should they divide and multiply? When should they give up their stem-ness, instead transforming into oxygen-carrying red blood cells or white blood cells, the immune defenders?

Both new studies took aim at cracking the elusive curriculum.

In the first study, Daley and team started with human skin and other cells that have been transformed back into stem cells (dubbed iPSCs, or induced pluripotent stem cells). Although iPSCs theoretically have the ability to turn into any cell type, no one has previously managed to transform them into blood stem cells.

A lot of people have become jaded, saying that these cells dont exist in nature and you cant just push them into becoming anything else, says Bhatia.

All cells in an organism share the same genes. However, for any given cell only a subset of genes are turned into proteins. This process is what gives cells their identitiesmay it be a heart cell, liver cell, or blood stem cell.

Daley and team focused on a family of transcription factors. Similar to light switches, these proteins can flip genes on or off. By studying how blood vessels normally give birth to blood stem cells, they found seven factors that encouraged iPSCs to grow into immature blood stem cells.

Using a virus, the team inserted these factors into their iPSCs and injected the transformed cells into the bone marrow of mice. These mice had been irradiated to kill off their own blood stem cells to make room for the lab-grown human replacements.

In this way, Daley exposed the immature cells to signals in a blood stem cells normal environment. The bone marrow acts like a school, explains Drs. Carolina Guibentif and Berthold Gttgens at the University of Cambridge, who are not involved in the study.

It worked. In just twelve weeks, the lab-made blood stem cells had fully matured into master cells capable of making the entire range of cells normally found in human blood. Whats more, when scientists took these cells out and transplanted them into a second recipient, they retained their power.

This a major step forward compared with previous methods, says Guibentif.

In contrast, the second study took a more direct route. Rafii and team took cells lining a mouses vessels, based on the finding that these cells normally turn into blood stem cells during development.

With a set of four transcription factors, the team directly reprogrammed them into baby blood stem cells, bypassing the iPSC stage.

These factors act like a maternity ward, allowing the blood stem cells to be born, says Guibentif.

To grow them to adulthood, Rafii and team laid the cells onto a blanket of supporting cells that mimics the blood vessel nursery. Under the guidance of molecular cues secreted by these supporting cells, the blood stem cells multiplied and matured.

When transplanted into short-lived mice without a functional immune system, the cells sprung to action. In 20 weeks, the mice generated an active immune response when given a vaccine. Whats more, they went on to live a healthy 1.5 yearsroughly equivalent to 60 years old for a human.

Rafii is especially excited about using his system to finally crack the stem cell learning curriculum.

If we can figure out the factors that coax stem cells to divide and mature, we may be able to unravel the secrets of their longevity and make full-fledged blood stem cells in a dish, he says.

Calling both experiments a breakthrough, Guibentif says, this is something people have been trying to achieve for a long time.

However, she points out that both studies have caveats. A big one is cancer. The transcription factors that turn mature cells into stem cells endow them with the ability to multiply efficientlya hallmark of cancerous cells. Whats more, the virus used to insert the factors into cells may also inadvertently turn on cancer-causing genes.

That said, neither team found evidence of increased risk of blood cancers. Guibentif also acknowledges that future studies could use CRISPR in place of transcription factors to transform cells into blood stem cells on demand, further lowering the risk.

The techniques will also have to be made more efficient to make lab-grown blood stem cells cost efficient. Itll be years until human use, says Guibentif.

Even so, the studies deter even the most cynical of critics.

After 20 years, were finally tantalizingly close to generating bona fide human blood stem cells in a dish,"says Daley.

Image Credit: Pond5

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Malaria parasites (green) are killing this red blood cell, but a new study suggests they also damage bone.

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By Mitch LeslieJun. 2, 2017 , 2:00 PM

Malaria parasites leave a trail of destruction in an infected persons body. The microscopic invaders massacre red blood cells, produce harmful chemicals, and sometimes damage the brain. A new mouse study suggests that the parasites can also weaken bones. If they do the same in people, they could stunt the growth of children infected with the disease. But the study also provides some good news, identifying a potential way to prevent the skeletal decline with a compound similar to vitamin D.

Its important work, says parasitologist Regina Joice Cordy of Emory University in Atlanta, who wasnt connected to the study. Its taken us a step further, she adds, in understanding the long-term effects of malaria infections.

Malaria parasites, which are transmitted through the bite of an infected mosquito, cause the most destruction during the part of their life cycle when they dwell in red blood cells circulating through the body. There, they reproduce and feast on oxygen-carrying hemoglobin proteins, releasing noxious byproducts. The parasites eventually explode from the blood cells, killing them in droves. Although researchers have also detected the parasites in bone marrow, where blood-forming stem cells reside, no one has known until now whether they damage the skeleton.

To find out, a team led by graduate student Michelle Lee and immunologist Cevayir Coban of Osaka University in Japan infected mice with either of two species of malaria parasites. The rodents immune systems fought off the parasites, but the animals skeletons showed the effects of the infection. We found bone loss for both types of infections, Coban says. In adult mice, the spongy material inside the bones began to break down. It contained more gaps, and support structures were thinner and less numerous. Similar changes occur in the bones of people with osteoporosis, Coban says.

In young mice, the bones also grew slower than normal. As a result, the animals thigh bones were about 10% shorter than those of their uninfected counterparts, the researchers report online today in Science Immunology.

The parasites might trigger these problems, the scientists hypothesized, by upsetting the normal balance between cells known as osteoclasts, which dissolve bone, and cells called osteoblasts, which build it back up. The researchers discovered that both types of cells shut down when the mice were infected with malaria. Once the animals had eliminated the parasites, both cell types started working again. But bone breakdown outpaced bone restoration, suggesting that osteoclasts were working harder.

Why do the mices bones deteriorate even after their immune system ousted the parasites? Lee, Coban, and colleagues suspected that the culprit was chemical waste released by the parasites, including the residue of digested hemoglobin, a molecule called hemozoin. In malaria-infected mice, the researchers found, hemozoin seeped into the bones, turning them black. It was still there 2 months after the parasites had been eliminated. To gauge the impact of hemozoin and other parasite wastes, the team cultured bone marrow cells in a cocktail of these substances. The mixture spurred the cells to release inflammation-promoting molecules known to spur osteoclast production.

That mechanism suggested a way to block the parasites bone-destroying effects. Coban and colleagues gave infected mice alfacalcidol, a derivative of vitamin D that treats osteoporosis by suppressing osteoclasts and stimulating osteoblasts. The drug prevented bone loss in the mice.

Cordy says the proposed bone-destroying mechanism is plausible. The key question, she says, is whether it occurs in humans. So far, Coban says, the researchers dont have direct evidence that malaria triggers bone loss in people. Children in malaria-prone areas often grow abnormally slowly, but researchers arent sure whether malaria or other diseases that are prevalent in these areas are to blame. If further studies confirm the new findings, treating kids with alfacalcidol or related molecules, along with antimalarials, might lead to a growth spurt.

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Malaria may weaken the skeleton - Science Magazine

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