He was tired of the daily pain that made even shaking someone's hand almost unbearable.

Marlette lost his arm in an accident when he was a teenager, but as an active kid, he didn't this slow him down. He continued to play football and golf, running track and even wrestling.

But over time, the strain on his remaining arm and wrist took a toll.

So to relieve his pain, he traveled from Sioux Falls, South Dakota, to Munich, Germany, with the hopes that a special procedure using stem cells could make a difference.

"There's no cartilage," Marlette said of his wrist. "I'm bone-on-bone. It is constantly inflamed and very sore."

As Marlette grew older, even the simplest things, like tucking in his shirt or putting on a jacket, became incredibly painful.

Marlette developed cysts and holes in the bones of his wrist. Doctors prescribed anti-inflammatory medications, but they only managed the pain, doing nothing to actually heal the problem. One day, his doctor, Dr. Bob Van Demark at Sanford Health in South Dakota, where Marlette works in finance, saw a presentation by Dr. Eckhard Alt.

It was about a new treatment using stem cells.

"Following an infection or wound or trauma," Alt said, "there comes a call to the stem cells in the blood vessels, which are silent, and nature activates those cells."

Stem cells are located throughout our bodies, like a reserve army offering regeneration and repair. When we're injured or sick, our stem cells divide and create new cells to replace those that are damaged or killed. Depending on where the cells are in the body, they adapt, becoming specialized as blood cells, muscle cells or brain cells, for example.

Alt was the first person to use adipose tissue, or fat, as a prime source of stem cells, according to Dr. David Pearce, executive vice president for research at Sanford health.

"He observed that the simplest place to get some stem cells is really from the fat," said Pearce. "Most of us could give some fat up, and those stem cells don't have to be programmed in any way, but if you put in the right environment, they will naturally turn into what the cell type around them is."

Fat tissue has a lot of blood vessels, making it a prime source of stem cells, and Alt recognized that stem cells derived from adipose tissue are also particularly good at becoming cartilage and bone.

Bone marrow is another source of stem cells, but these easily turn into blood and immune cells. Stem cells from fat have another fate.

"Fat-derived stem cells have a different lineage they can turn into, that is really cartilage and bone and other sort of connective tissues," said Pearce.

Van Demark traveled to Alt's Munich clinic along with some doctors from Sanford, which is now partnering with Alt on clinical trials in the United States. Marlette's doctor was impressed with what he saw and recommended the treatment to his patient.

Marlette paid his own way to Munich, where he would receive an injection of stem cells from his own fat tissue.

"I had one treatment, and my wrist felt better almost within the next couple weeks," Marlette said. "Through the course of the next seven months, it continued to feel better and better."

One injection was enough for this ongoing improvement.

"We see (from an MRI scan) that those cysts are gone, the bone has restructured, the inflammation is gone, and he formed ... new cartilage," said Alt.

MRIs confirmed what he was feeling: The cartilage had begun to regenerate in his wrist. Because the procedure uses autologous cells, which are cells from the patient's own body, there's little to no chance of rejection by the body's immune system.

Though the procedure worked for Marlette, the use of stem cells as a form of treatment is not without controversy or risk. In the US, they have been mired in controversy because much of the early research and discussion has been centered around embryonic and fetal stem cells.

Marlette traveled to Germany because approved treatments like this are not available in the United States. Clinics have popped up across the country, but they lack oversight from the Food and Drug Administration.

Dr. Robin Smith, founder of the Stem for Life Foundation, first began working in this field 10 years ago. According to Smith, there were 400 clinical trials for stem cells when she first started; now, there are 4,500. She partnered with the Vatican to hold a stem cell conference last year.

"We're moving toward a new era in medicine," said Smith, who was not involved in this research. "(We are) recognizing cells in our body and immune system can be used in some way -- manipulated, redirected or changed at the DNA level -- to impact health and cure disease. It is an exciting time."

Dr. Nick Boulis is a neurosurgeon with Emory University in Atlanta. His team ran the first FDA-approved clinical trials in the US to inject stem cells in the spinal cords of patients with ALS, better known as Lou Gehrig's disease, and he isn't surprised to see procedures like the one at Alt's clinic in Germany have success.

"Joints and bones heal," Boulis said. "The nervous system is very bad at healing. It doesn't surprise me that we're seeing successes in recapitulating cartilage before we're seeing successes in rebuilding the motherboard."

Smith also cautioned patients to do their research, especially about the types of cells being used. "When you have a health problem, and you need a solution, sometimes you don't have three five, seven years to get there," she said, referencing the slow progression of regulations in places like the United States.

"So really ,look for places that have the regulatory approval of the country they're in. Safety has to be number one," she said.

Alt's Munich clinic was approved by the European equivalent of the FDA, the European Medicines Agency. Through the partnership with Sanford, the health group is now launching clinical trials in America, focusing on rotator cuff injuries, a common shoulder injury. This is the first FDA-approved trial of its kind.

Further down the line, Alt hopes to see stem cells used for such issues as heart procedures and treating the pancreas to help diabetics. For him, the growth is limitless.

"I think it will be exponential," he said. "It will be the same thing (we saw) with deciphering the human genome. The knowledge will go up exponentially, and the cost will go exponentially down. For me, the most exciting thing is to see how you can help patients that have been desperate for which there was no other option, no hope, and how well they do."

For Marlette, it has meant a wrist free from pain and a life free from pain medication.

Since the procedure in August, he hasn't taken any of the anti-inflammatory drugs. "I have more range of motion with my wrist, shaking hands didn't hurt anymore," he said. "My wrist seems to continue to improve, and there's less and less pain all the time."

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Patient uses fat stem cells to repair his wrist - CNN

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Nearly 40 years after the world was jolted by the birth of the first test-tube baby, a new revolution in reproductive technology is on the horizon and it promises to be far more controversial than in vitro fertilization ever was.

Within a decade or two, researchers say, scientists will likely be able to create a baby from human skin cells that have been coaxed to grow into eggs and sperm and used to create embryos to implant in a womb.

The process, in vitro gametogenesis, or I.V.G., so far has been used only in mice. But stem cell biologists say it is only a matter of time before it could be used in human reproduction opening up mind-boggling possibilities.

With I.V.G., two men could have a baby that was biologically related to both of them, by using skin cells from one to make an egg that would be fertilized by sperm from the other. Women with fertility problems could have eggs made from their skin cells, rather than go through the lengthy and expensive process of stimulating their ovaries to retrieve their eggs.

It gives me an unsettled feeling because we dont know what this could lead to, said Paul Knoepfler, a stem cell researcher at UC Davis. You can imagine one man providing both the eggs and the sperm, almost like cloning himself. You can imagine that eggs becoming so easily available would lead to designer babies.

Some scientists even talk about what they call the Brad Pitt scenario when someone retrieves a celebritys skin cells from a hotel bed or bathtub. Or a baby might have what one law professor called multiplex parents.

There are groups out there that want to reproduce among themselves, said Sonia Suter, a George Washington University law professor who began writing about I.V.G. even before it had been achieved in mice. You could have two pairs who would each create an embryo, and then take an egg from one embryo and sperm from the other, and create a baby with four parents.

Three prominent academics in medicine and law sounded an alarm about the possible consequences in a paper published this year.

I.V.G. may raise the specter of embryo farming on a scale currently unimagined, which might exacerbate concerns about the devaluation of human life, Dr. Eli Y. Adashi, a medical science professor at Brown; I. Glenn Cohen, a Harvard Law School professor; and Dr. George Q. Daley, dean of Harvard Medical School, wrote in the journal Science Translational Medicine.

Still, how soon I.V.G. might become a reality in human reproduction is open to debate.

I wouldnt be surprised if it was five years, and I wouldnt be surprised if it was 25 years, said Jeanne Loring, a researcher at The Scripps Research Institute in La Jolla who, with the San Diego Zoo, hopes to use I.V.G. to increase the population of the nearly extinct northern white rhino.

Loring said that when she discussed I.V.G. with colleagues who initially said it would never be used with humans, their skepticism often melted away as the talk continued. But not everyone is convinced that I.V.G. will ever become a regularly used process in human reproduction even if the ethical issues are resolved.

People are a lot more complicated than mice, said Susan Solomon, chief executive of the New York Stem Cell Foundation. And weve often seen that the closer you get to something, the more obstacles you discover.

I.V.G. is not the first reproductive technology to challenge the basic paradigm of baby-making. Back when in vitro fertilization was beginning, many people were horrified by the idea of creating babies outside the human body. And yet, I.V.F. and related procedures have become so commonplace that they now account for about 70,000, or almost 2 percent, of the babies born in the United States each year. According to the latest estimate, there have been more than 6.5 million babies born worldwide through I.V.F. and related technologies.

Of course, even I.V.F. is not universally accepted. The Catholic Church remains firm in its opposition to in vitro fertilization, in part because it so often leads to the creation of extra embryos that are frozen or discarded.

I.V.G. requires layers of complicated bioengineering. Scientists must first take adult skin cells other cells would work as well or better, but skin cells are the easiest to get and reprogram them to become embryonic stem cells capable of growing into different kinds of cells.

Then, the same kind of signaling factors that occur in nature are used to guide those stem cells to become eggs or sperm. (Cells taken from women could be made to produce sperm, the researchers say, but the sperm, lacking a Y chromosome, would produce only female babies.)

Last year, researchers in Japan, led by Katsuhiko Hayashi, used I.V.G. to make viable eggs from the skin cells of adult female mice, and produced embryos that were implanted into female mice, who then gave birth to healthy babies.

The process strikes some people as inherently repugnant.

There is a yuck factor here, said Arthur Caplan, a bioethicist at New York University. It strikes many people as intuitively yucky to have three parents, or to make a baby without starting from an egg and sperm. But then again, it used to be that people thought blood transfusions were yucky, or putting pig valves in human hearts.

Whatever the social norms, there are questions about the wisdom of tinkering with basic biological processes. And there is general agreement that reproductive technology is progressing faster than consideration of the legal and ethical questions it raises.

We have come to realize that scientific developments are outpacing our ability to think them through, Adashi said. Its a challenge for which we are not fully prepared. It would be good to be having the conversation before we are actually confronting the challenges.

Some bioethicists take the position that while research on early stages of human life can deepen the understanding of our genetic code, tinkering with biological mechanisms that have evolved over thousands of years is inherently wrongheaded.

Basic research is paramount, but its not clear that we need new methods for creating viable embryos, said David Lemberg, a bioethicist at National University in California. Attempting to apply what weve learned to create a human zygote is dangerous, because we have no idea what were doing, we have no idea what the outcomes are going to be.

Lewin writes for The New York Times.

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Growing an entire baby from skin cells could happen in a decade ... - The San Diego Union-Tribune

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Rio Sugimura

Researchers made these blood stem cells and progenitor cells from human induced pluripotent stem cells.

After 20 years of trying, scientists have transformed mature cells into primordial blood cells that regenerate themselves and the components of blood. The work, described today in Nature1, 2, offers hope to people with leukaemia and other blood disorders who need bone-marrow transplants but cant find a compatible donor. If the findings translate into the clinic, these patients could receive lab-grown versions of their own healthy cells.

One team, led by stem-cell biologist George Daley of Boston Childrens Hospital in Massachusetts, created human cells that act like blood stem cells, although they are not identical to those found in nature1. A second team, led by stem-cell biologist Shahin Rafii of Weill Cornell Medical College in New York City, turned mature cells from mice into fully fledged blood stem cells2.

For many years, people have figured out parts of this recipe, but theyve never quite gotten there, says Mick Bhatia, a stem-cell researcher at McMaster University in Hamilton, Canada, who was not involved with either study. This is the first time researchers have checked all the boxes and made blood stem cells.

Daleys team chose skin cells and other cells taken from adults as their starting material. Using a standard method, they reprogrammed the cells into induced pluripotent stem (iPS) cells, which are capable of producing many other cell types. Until now, however, iPS cells have not been morphed into cells that create blood.

The next step was the novel one: Daley and his colleagues inserted seven transcription factors genes that control other genes into the genomes of the iPS cells. Then they injected these modified human cells into mice to develop. Twelve weeks later, the iPS cells had transformed into progenitor cells capable of making the range of cells found in human blood, including immune cells. The progenitor cells are tantalizingly close to naturally occurring haemopoetic blood stem cells, says Daley.

Bhatia agrees. Its pretty convincing that George has figured out how to cook up human haemopoetic stem cells, he says. That is the holy grail.

By contrast, Rafiis team generated true blood stem cells from mice without the intermediate step of creating iPS cells. The researchers began by extracting cells from the lining of blood vessels in mature mice. They then inserted four transcription factors into the genomes of these cells, and kept them in Petri dishes designed to mimic the environment inside human blood vessels. There, the cells morphed into blood stem cells and multiplied.

When the researchers injected these stem cells into mice that had been treated with radiation to kill most of their blood and immune cells, the animals recovered. The stem cells regenerated the blood, including immune cells, and the mice went on to live a full life more than 1.5 years in the lab.

Because he bypassed the iPS-cell stage, Rafii compares his approach to a direct aeroplane flight, and Daleys procedure to a flight that takes a detour to the Moon before reaching its final destination. Using the most efficient method to generate stem cells matters, he adds, because every time a gene is added to a batch of cells, a large portion of the batch fails to incorporate it and must be thrown out. There is also a risk that some cells will mutate after they are modified in the lab, and could form tumours if they are implanted into people.

But Daley and other researchers are confident that the method he used can be made more efficient, and less likely to spur tumour growth and other abnormalities in modified cells. One possibility is to temporarily alter gene expression in iPS cells, rather than permanently insert genes that encode transcription factors, says Jeanne Loring, a stem-cell researcher at the Scripps Research Institute in La Jolla, California. She notes that iPS cells can be generated from skin and other tissue that is easy to access, whereas Rafiis method begins with cells that line blood vessels, which are more difficult to gather and to keep alive in the lab.

Time will determine which approach succeeds. But the latest advances have buoyed the spirits of researchers who have been frustrated by their inability to generate blood stem cells from iPS 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, Bhatia says. I hoped the critics were wrong, and now I know they were.

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Lab-grown blood stem cells produced at last - Nature.com

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Boston, MA (UroToday.com) The risk of erectile dysfunction (ED) increases with age and typically occurs in middle and older aged men. Dr. Mazur presented a study on young men referred with ED with symptoms of low testosterone. The authors aimed to describe the hormonal profiles of young men with the chief complaint of ED, hypothesizing that the majority of young men with ED will have normal hormonal evaluations.

This was a retrospective single center study of men aged 18-40 years who presented with the complaint of ED and had a hormonal evaluation from 2002- 2016 at a tertiary care institution. Data on demographics, co-morbidities, medications, and hormonal evaluations was obtained for all patients. Hypogonadism was defined as a testosterone level <200 ng/dL and hyperprolactinemia as a prolactin level >13.1 ng/mL.

A total of 2,292 relevant men were identified. The median age was 32.7 years with a larger proportion complaining of ED as they neared age 40 compared to younger ages. 43% of men were White, 8.6% Black, 4% Asian, 0.9% Hispanic, and 43.6% other or unknown. Median BMI was 26.8. Some of the men took medication on a regular basis that have been linked to ED including anti-hypertensives, antihistamines, and H2-receptor antagonists. The average total testosterone level was 368 160 ng/dL. 10.6% of men had hypogonadism and 8.5% of men had hyperprolactinemia. Abnormalities of LH and FSH were noted in 10% and 9.1% of men, respectively. Regarding their ED treatment, 68.7% of men were given a phosphodiesterase type 5 inhibitor (PDE5i) and 2.4% were given alprostadil. Lastly, 12.9% of men were started on testosterone therapy.

The majority of men under age 40 with ED exhibit a normal hormonal milieu. Additionally, many men were using medications that have been linked to ED. Most men with ED were treated with a PDE5i.

Presented By: Daniel J. Mazur, Chicago, IL

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 Boston, Massachusetts, USA

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AUA 2017: Prevalence of Hormonal Abnormalities in Young Men with Erectile Dysfunction - UroToday

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Boston, MA (UroToday.com) Libido is thought to be influenced by hormonal milieu, particularly testosterone. The knowledge about the role of estradiol in male sexual function has been found to be more important than originally thought. The estradiol cut-off point of 5 ng/dL in hypogonadal men is thought to directly affect libido. Dr. Gupta presented a study assessing the impact of sex hormones on libido specifically in a cardiac patient population.

The study focused on 200 men in a cardiology practice who completed the IIEF-15, ADAM, and previous ED treatment questionnaires. Additionally all patients had serum total testosterone (T), estradiol (E), and sex hormone binding globulin (SHBG) levels measured via morning lab draws. Their free testosterone (CFT) was calculated using an online ISSM calculator. Patients that were diagnosed for hypogonadism in the past or who were currently on medications possibly affecting T levels were excluded. Hormonal levels were correlated to responses to the IIEF questions 11 and 12 (IIEF11, IIEF12), focusing on libido.

Results demonstrated the mean total T level to be 310 ng/dL with CFT of 5.4 ng/dL. Mean E levels were 4.4 ng/dL and mean T:E ratio was 8.2. Importantly, 55% of patients had T levels less than 300 ng/dL and 74% of patients had a CFT < 6.5 ng/dL. Negative correlation was found between estradiol and IIEF11 and IIEF12, but was not statistically significant. However, a positive correlation was found between IIEF11 and IIEF12 and CFT and T:E ratio (p=0.007, p=0.009, respectively). At a cutoff of E=5ng/dL, no difference was found for either hypogonadal or eugonadal men on the IIEF11 or IIEF12.

In summary, CFT and T:E ratio were predictive of positive libido response on IIEF11 & 12 questions in the IIEF questionnaire. Estradiol, even at a cutoff of 5 ng/dL, was not independently associated with improved libido. Surprisingly, no correlation was found between total testosterone and IIEF11 (desire frequency). The effect of testosterone and estradiol on libido requires further research with prospective studies.

Presented By: Nikhil Gupta, Springfield, IL

Written By: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre

at the 2017 AUA Annual Meeting - May 12 - 16, 2017 Boston, Massachusetts, USA

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AUA 2017: Calculated Free T and T:E Ratio but not Total Testosterone and Estradiol Predict Low Libido - UroToday

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By Anette Breindl Senior Science Editor

"With the advent of targeted cancer therapies, what we've found is that many of them are cardiotoxic," Saptarsi Haldar told BioWorld Today. "Pathways that are effective in cancer are toxic in the heart."

In the May 17, 2017, issue of Science Translational Medicine, Haldar, who is an associate investigator at the Gladstone Institute of Cardiovascular Disease, and his colleagues showed that a class of epigenetic drugs, the BET bromodomain inhibitors, may be not just an exception to that rule, but a class of drugs that has therapeutic utility in heart failure.

The team showed that the bromodomain inhibitor JQ-1 had therapeutic benefits in two separate animal models of advanced heart failure, but did not affect the beneficial changes to heart muscle cells that are a consequence of exercise.

The paper shows a potential new approach to heart failure an indication that, with a five-year survival rate of 60 percent, needs them.

It also shows a potential approach to another vexing problem, namely drugging transcription factors.

"There's a surprisingly tractable therapeutic index for drugging transcription in diseases," Haldar said.

While BRD4 is not itself a transcription factor, inhibiting it "dampens the transcription factor-driven network that's driving the disease . . . This is really about dampening transcriptional rewiring," he added.

In heart failure, those happen to be innate immune signaling and fibrotic signaling. Experiments in cardiac cells derived from induced pluripotent stem cells (iPSCs) showed that JQ-1 acted by blocking the activation of innate immune and profibrotic pathways, essentially preventing heart cells from rewiring themselves in maladaptive ways in response to being chronically overworked.

Haldar said the original idea to test whether the compound would have an effect in heart failure was based on "an educated guess."

Previous work had shown that certain epigenetic marks, namely acetyl marks on lysines, play a role in heart failure.

"There is a lot known about lysine acetylation in heart failure," Haldar said, and there had been previous attempts at targeting the process, which had "fallen to the wayside, in part because of issues with therapeutic index."

Even studying the molecular details of lysine acetylation's role in heart failure was challenging, because genetic approaches are not viable.

The problem became tractable with the synthesis of JQ-1 in the laboratory of James Bradner, who is a co-author on the Science Translational Medicine paper. The compound, which has been used to gain insight into epigenetic aspects of a large number of biological processes thanks to the decision of its developers to distribute it freely, targets BRD4, a "reader" protein that recognizes acetylated lysines. (See BioWorld Insight, Aug. 12, 2013.)

With the advent of JQ-1, Haldar said, "we immediately made the connection that here's a target BRD4 that you could specifically modulate that is recognizing acetyl-lysines on chromatin."

The team initially published work in 2013 showing that JQ-1 affected cellular processes in heart failure, and was an effective therapeutic in mice when given very early in the disease.

Patients, though, don't show up in their doctor's office very early in the disease. They show up with "pre-existing, often chronic heart failure," Haldar said.

At that point, the heart has already undergone significant remodeling that includes fibrosis and an activation of innate immune pathways.

The work now published in Science Translational Medicine showed that JQ-1 had effects even when given to mice that had established heart failure either due to a heart attack, or pressure overload, but did not block exercise-induced remodeling.

The team is hoping to test JQ-1 derivatives in large animal models, and ultimately take them into the clinic. Haldar is a co-founder of Tenaya Therapeutics Inc., a company launched in December with a $50 million series A financing from The Column Group. Haldar said that while he holds a patent on BET protein inhibition in heart disease, BET proteins are only "one of many targets/pathways that Tenaya is considering."

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Researchers show cancer drug class has cardiac benefits - BioWorld Online

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With gene-editing techniques such as CRISPR-Cas9, offending genes could one day be snipped out of hematopoietic stem cells, then be returned to their owners to generate new lines of disease-free blood cells

New research has nudged scientists closer to one of regenerative medicines holy grails: the ability to create customised human stem cells capable of forming blood that would be safe for patients. Advances reported in the journal Nature could not only give scientists a window on what goes wrong in such blood cancers as leukaemia, lymphoma and myeloma, but they could also improve the treatment of those cancers, which affect some 1.2 million Americans. The stem cells that give rise to our blood are a mysterious wellspring of life. In principle, just one of these primitive cells can create much of a human beings immune system, not to mention the complex slurry of cells that courses through a persons arteries, veins and organs. While the use of blood-making stem cells in medicine has been common since the 1950s, it remains pretty crude. After patients with blood cancers have undergone powerful radiation and chemotherapy treatments to kill their cancer cells, they often need a bone-marrow transplant to rebuild their white blood cells, which are destroyed by that treatment. The blood-making stem cells that reside in a donors bone marrow and in umbilical cord blood that is sometimes harvested after a babys birth are called hematopoietic, and they can be life-saving. But even these stem cells can bear the distinctive immune system signatures of the person from whom they were harvested. As a result, they can provoke an attack if the transplant recipients body registers the cells as foreign. This response, called graft-versus-host disease, affects as many as 70 percent of bone-marrow transplant recipients in the months following the treatment, and 40 percent develop a chronic version of the affliction later. It can overwhelm the benefit of a stem cell transplant. And it kills many patients. Rather than hunt for a donor whos a perfect match for a patient in need of a transplant a process that can be lengthy, ethically fraught and ultimately unsuccessful doctors would like to use a patients own cells to engineer the hematopoietic stem cells. The patients mature cells would be reprogrammed to their most primitive form: stem cells capable of becoming virtually any kind of human cell. Then factors in their environment would coax them to become the specific type of stem cells capable of giving rise to blood. Once reintroduced into the patient, the cells would take up residence without prompting rejection and set up a lifelong factory of healthy new blood cells. If the risk of deadly rejection episodes could be eliminated, physicians might also feel more confident treating blood diseases that are painful and difficult but not immediately deadly diseases such as sickle cell disease and immunological disorders with stem cell transplants. The two studies published on Wednesday demonstrate that scientists may soon be capable of pulling off the sequence of operations necessary for such treatments to move ahead. One of two research teams, led by stem cell pioneer Dr George Q. Daley of Harvard Medical School and the Dana Farber Cancer Institute in Boston, started their experiment with human pluripotent stem cells primitive cells capable of becoming virtually any type of mature cell in the body. Some of them were embryonic stem cells and others were induced pluripotent stem cells, or iPS cells, which are made by converting mature cells back to a flexible state. The scientists then programmed those pluripotent stem cells to become endothelial cells, which line the inside of certain blood vessels. Past research had established that those cells are where blood-making stem cells are born. Here, the process needed a nudge. Using suppositions gleaned from experiments with mice, Daley said his team confected a special sauce of proteins that sit on a cells DNA and programme its function. When they incubated the endothelial cells in the sauce, they began producing hematopioetic stem cells in their earliest form. Daleys team then transferred the resulting blood-making stem cells into the bone marrow of mice to see if they would take. In two out of five mice who got the most promising cell types, they did. Not only did the stem cells establish themselves, they continued to renew themselves while giving rise to a wide range of blood cells. A second research team, led by researchers from Weill Cornell Medicines Ansary Stem Cell Institute in New York, achieved a similar result using stem cells from the blood-vessel lining of adult mice. After programming those cells to revert to a more primitive form, the scientists also incubated those stem cells in a concoction of specialised proteins. When the team, led by Raphael Lis and Dr Shahin Rafii, transferred the resulting stem cells back into the tissue lining the blood vessels of the mice from which they came, that graft also took. For at least 40 weeks after the incubated stem cells were returned to their mouse owners, the stem cells continued to regenerate themselves and give rise to many blood-cell types without provoking immune reactions. In addition to making a workhorse treatment for blood cancers safer, the new advances may afford scientists a unique window on the mechanisms by which blood diseases take hold and progress, said Lee Greenberger, chief scientific officer for the Leukemia and Lymphoma Society. From a research point of view you could now actually begin to model diseases, said Greenberger. If you were to take the cell thats defective and make it revert to a stem cell, you could effectively reproduce the disease and watch its progression from the earliest stages. That, in turn, would make it easier to narrow the search for drugs that could disrupt that disease process early. And it would speed the process of discovering which genes are implicated in causing diseases. With gene-editing techniques such as CRISPR-Cas9, those offending genes could one day be snipped out of hematopoietic stem cells, then be returned to their owners to generate new lines of disease-free blood cells. But Daley cautioned that significant hurdles remain before studies like these will transform the treatment of blood diseases. We do know the resulting cells function like blood stem cells, but they still are at some distance, molecularly, from native stem cells, he said. By tinkering with the processes by which pluripotent stem cells mature into blood-producing stem cells, Daley said his team hopes to make these lab-grown cells a better match for the real things. Los Angeles Times/TNS

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Regenerative medicine: holy grail within grasp? - Gulf Times

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Science World Report

Bone Marrow Stem Cell Transplants Could Advance ALS Treatment Science World Report The researchers discovered that bone marrow stem cell transplants may advance the treatment of the disease amyotrophic lateral sclerosis (ALS). The transplants enhanced the motor functions and nervous system conditions in mice with ALS that modeled in ... Stem cell transplants beneficial to mice with ALSLife Science Daily all 2 news articles »

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Bone Marrow Stem Cell Transplants Could Advance ALS Treatment - Science World Report

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Its one of those times when serendipity went to work. As a team of UT Southwestern Medical Center researchers were studying a rare form of genetic cancer called Neurofibromatosis Type 1 that causes tumors to grow on nerves, what they discovered instead were hair progenitor cells. Essentially, these are the cells that cause hair to grow. With this new information on hand, the path towards managing hair growth problems, including hair discoloration (a.k.a greying of hair) now seems to have become clearer.

As explained by Dr. Lu Le, one of the researchers and currently an Associate Professor of Dermatology: With this knowledge, we hope in the future to create a topical compound or to safely deliver the necessary gene to hair follicles to correct these cosmetic problems.

Prior to this discovery, researchers were already aware that skin stem cells located in the bulge on bottom of hair follicles were involved, in one way or another, in the growth of hair. What they didnt know was how these skin cells turn into hair cells, specifically, what happens after those cells move down to the bulb or the base of hair follicles. This also meant they had no idea what to do to stimulate and manipulate their growth.

As they were studying the nerve cells and how tumors formed on them, they discovered a protein that differentiates the skin stem cells from other types of cells. The protein is called KROX20 and as far as they knew, this protein was more commonly associated with nerve development. In the hair follicles of their mice test subjects, however, they found out that KROX20 becomes activated in the skin cells which eventually turn into hair shafts that cause hair to grow. That said, though, its not as simple as that.

It turned out that KROX20 works in tandem with another protein called SCF (short for stem cell factor) and without either one, hair growth happens abnormally, or not at all.

When KROX20 turns on in a skin cell, it causes the cell to produce SCF. With both proteins now active, they move up the hair bulb, interact with melanocyte cells (the cells that produce pigment), and grow into healthy, colored hairs.

When the team removed the KROX20-producing cells, the mice did not grow any hair, meaning, they became bald. And when they removed the SCF gene, the mices hair started out as gray-colored, then turned white with age.

From these results, the obvious way forward is to backtrack whats happening, possibly try to figure out why and how aging affects KROX20 protein production. Another aspect that will also be looked at is the reason why the SCF gene stops functioning, thereby resulting in gray hair production. The findings could also help provide answers on why hair loss and graying of hair are among the first indications of aging.

The research was recently published in the journal Genes & Development.

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Cells Responsible for Hair Growth Discovered - Wall Street Pit

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By 2040, there will be 9 billion people in the world. Thats like adding another China onto todays global population, said Professor Sophien Kamoun of the Sainsbury Laboratory in Norwich, UK.

Prof. Kamoun is one of a growing number of food scientists trying to figure out how to feed the world. As an expert in plant pathogens such asPhytophthora infestans the fungus-like microbe responsible for potato blight he wants to make crops more resistant to disease.

Potato blight sparked the Irish famine in the 19th century, causing a million people to starve to death and another million migrants to flee. European farmers now keep the fungus in check by using pesticides. However, in regions without access to chemical sprays, it continues to wipe out enough potatoes to feed hundreds of millions of people every year.

Potato blight is still a problem, said Prof. Kamoun. In Europe, we use 12 chemical sprays per season to manage the pathogen that causes blight, but other parts of the world cannot afford this.

Plants try to fight off the pathogens that cause disease but these are continuously changing to evade detection by the plants immune system.

Arms race

In nature, every time a plant gets a little better at fighting off infection, pathogens adapt to evade their defences. Now biologists are getting involved in the fight.

Its essentially an arms race between plants and pathogens, said Prof. Kamoun. We want to turn it into an arms race between biotechnologists and pathogens by generating new defences in the lab.

If we think of the genome as text, CRISPR is a word processor that allows us to change just a letter or two.

Prof. Sophien Kamoun, Sainsbury Laboratory, UK

Five years ago, Prof. Kamoun embarked on a project called NGRB, funded by the EU's European Research Council. The plan was to find a way to make potatoes more resistant to infection using advanced plant-breeding techniques.

Then serendipity struck. In the early stages of the project, scientists in another lab discovered a ground-breaking gene-editing technique known as CRISPR-Cas which allows scientists to delete or add genes at will. As well as having potential medical applications in humans, this powerful tool is unlocking new approaches to perfecting plants.

If we think of the genome as text, CRISPR is a word processor that allows us to change just a letter or two, explained Prof. Kamoun. The precision that this allows makes CRISPR the ultimate in genetic editing. Its really beautiful.

One of the simplest ways to use CRISPR to improve plants is to remove a gene that makes them vulnerable to infection. This alone can make potatoes more resilient, helping to meet the worlds growing demand for food.

The resulting crop looks and tastes just the same as any other potato. Prof. Kamoun says that potatoes which are missing a gene or two should not be viewed in the same way as genetically modified foods which sometimes contain genes introduced from another species. Its a very important technical difference but not all regulators have updated their rules to make this distinction.

Potatoes are not the only food crops that can be improved by CRISPR-Cas. Prof. Kamoun is now working on a project that aims to protect wheat from wheat blast a fungal disease decimating yields in Bangladesh and spreading in Asia.

Looking ahead, CRISPR will be used to improve the quality and nutritional value of wheat, rice, potatoes and vegetables. It could even be used to remove genes that cause allergic reactions in people with tomato or wheat intolerance.

If we can remove allergens, consumers may soon see hypoallergenic tomatoes on supermarket shelves, Prof. Kamoun said. Its a very exciting technology.

While targeting disease in this way could be a game changer for global food security in the years ahead, experts believe other approaches to plant breeding will continue to have a role. Understanding meiosis a type of cell division that can reshuffle genes to improve plants can help farmers and the agribusiness sector select for hardier crops, according to Professor Chris Franklin of the University of Birmingham, UK.

He leads the COMREC project, which trains young scientists to understand and manipulate meiosis in plants. The project applies the wealth of knowledge generated by leaders in the field to tackle the pressing problem of feeding a hungry world.

COMREC has begun to translate fundamental research into (applications in) key crop species such as cereals, brassicas and tomato, said Prof. Franklin. Close links with plant-breeding companies have provided important insight into the specific challenges confronted by the breeders.

Elite crops

There may be untapped potential in this approach to plant breeding: most of the genes naturally reshuffled during meiosis in cereal crops are at the far ends of chromosomes genes in the middle of chromosomes are rarely reshuffled, limiting the scope for new crop variations.

COMRECs academic and industry partners hope to understand why this is so that they can find a way to shuffle the genes in the middle of chromosomes too. And the food industry is keen to produce new elite varieties that are better adapted to confront the challenges arising from climate change, says Prof. Franklin.

A number of genes have now been identified that can make this reshuffling relatively more frequent, he said. CRISPR-Cas provides a way to modify the corresponding genes in crop species, helping to translate this basic research to target crops.

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Can CRISPR feed the world? | Horizon: the EU Research ... - Horizon magazine

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This week we went back to one of our favourite biotech hubs in the UK: Cambridge. Here, a young startup called Nemesis Bioscience is working on new treatment strategies to fight antimicrobial resistance based on CRISPR-Cas9.

Mission: Nemesis strategy is different from that of most companies in the antibiotic resistance space. Instead of developing new antibiotics to kill bacteria, the biotech aims to switch off resistance mechanisms and thereby resurrect antibiotic susceptibility. The Cybergenetics technologies use bacteriophages to deliver programmable RNA-guided endonucleases into the bacteria.

The nuclease can then inactivate antibiotic resistance genes and restore antibiotic activity. Nemesis first nuclease is directed against 8 families of beta-lactamases and is thereby able to inactivate resistance to beta-lactam antibiotics.

Comment: By targeting resistance genes directly, the biotech believes it is able to offset the natural selection pressure, which would eventually result in resistance to new antibiotic drugs. Swiss Bioversys is testing a similar approach, although the biotechs platform is based on small molecules.

Also, Nemesis technology represents yet another exciting therapeutic application of the CRISPR-Cas9 system. Because the endonuclease is delivered using bacteriophages, it is specifically targeted to bacteria, and not mammalian cells. Thereby, the technology overcomes the risk of off-target effects, which are currently limiting the therapeutic use of CRISPR.

Images via shutterstock.com / e X p o s e and nemesisbio.com

Merken

Continued here:

This UK Biotech uses CRISPR-Cas9 To Fight Bacterial Resistance - Labiotech.eu (blog)

Recommendation and review posted by simmons

In prepubertal patients with hypogonadism, treatment is directed at initiating pubertal development at the appropriate age. Age of therapy initiation takes into account the patient's psychosocial needs, current growth, and growth potential. Treatment entails hormonal replacement therapy with sex steroids, ie,estrogen for females and testosterone for males.

Introduction of sex steroids in such cases startswith the use ofsmall, escalating doses over a period of a couple of years. In females, introduction of puberty can begin with administration of small doses of estrogen given either orally or transdermally. One traditional regimen uses conjugated estrogen startingat doses as low as 0.15 mg daily and titrating upwards in 6-12 month intervals to typically 0.625 mg daily, at which point menses can be induced with the introduction of a progestin. Alternatively, transdermal 17-estradiol (0.08 to 0.12 mcg estradiol/kg) can be used.

In boys, introduction of puberty is achieved with the use of testosterone, administered intramuscularly or transdermally (in the form of a patch or gel). A typical regimen involves testosterone enanthate injections 50 mg monthly, titrating up to 200-250 mg every 2 weeks, which is a typical adult replacement dose. Adult testosterone dose can be adjusted to maintain serum testosterone concentrations in the normal adult range.

Therapy with sexsteroid replacement ensures development of secondary sexual characteristics and maintenance of normal sexual function. In patients with hypergonadotropic hypogonadism, fertility is not possible. However, patients with hypogonadotropic hypogonadism have fertilitypotential,although therapy with sex steroids does not confer fertility or stimulate testicular growth in men.An alternative for men with hypogonadotropic hypogonadism has been treatment with pulsatile LHRH or hCG, either of which can stimulate testicular growth and spermatogenesis.

Because such treatment is more complex than testosterone replacement, and because treatment with testosterone does not interfere with later therapy to induce fertility, most male patients with hypogonadotropic hypogonadism prefer to initiate and maintain virilization with testosterone.At a time when fertility is desired, it may be induced with either pulsatile LHRH or (more commonly) with a schedule of injections of hCG and FSH. Similarly, fertility can be achieved in females with pulsatile LHRH or exogenous gonadotropin. Such therapy results in ovulation in 95% of women.

A phase III, multicenter, open-label, single-arm trial by Nieschlag et al indicated that corifollitropin-alfa therapy combined with hCG treatment can significantly increase testicular volume and induce spermatogenesis in adult males with hypogonadotropic hypogonadism whose azoospermia could not be cured by hCG treatment alone. Patients in the study who remained azoospermic, though with normalized testosterone levels, after 16 weeks of hCG treatment underwent 52 weeks of twice-weekly hCG therapy along with every-other-week corifollitropin-alfa treatment (150 g). Mean testicular volume in these patients rose from 8.6 mL to 17.8 mL, while spermatogenesis was induced in more than 75% of subjects. [9]

The use of oral testosterone preparations, such as 17-alkylated androgens (eg, methyltestosterone), is discouraged because of liver toxicity. However, oral testosterone undecanoate is available in some countriesand is now approved in the United States. Intramuscular testosterone is available as testosterone enanthate or cypionate. Transdermal testosterone can be administered either in the form of a patch or gel. A nasal testosterone replacement therapy has been approved by the US Food and Drug Administration (FDA) for adult males with conditions such as primary hypogonadism (congenital or acquired) and hypogonadotropic hypogonadism (congenital or acquired) resulting from a deficiency or absence of endogenous testosterone. [10] The recommended dosage is 33 mg/day in three divided doses. The drug has not been approved for males younger than 18 years.

For older men with testosterone deficiency, a review by the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) found that the evidence concerning the risk of serious cardiovascular side effects from the use of testosterone in men with hypogonadism was inconsistent. [11, 12] The PRAC determined that the benefits of testosterone outweigh its risks but stressed that testosterone-containing medicines should be used only when lack of testosterone has been confirmed by signs and symptoms, as well as by laboratory tests. However,a literature review by Albert and Morley indicated that testosterone supplementation in males aged 65 years or older may increase the risk of cardiovascular events, particularly during the first year of treatment, althoughintramuscular testosterone seemed to carry less risk than other forms. [13]

On the other hand,a study by Traish et al suggested that long-term testosterone therapy in men with hypogonadism significantly reduces cardiovascular diseaserelated mortality. Patients in the studys testosterone-treated group (n=360) underwent therapy for up to 10 years, with median follow-up being 7 years. The investigators found no cardiovascular eventrelated deaths in the treated patients, compared with 19 such deaths in the group that received no testosterone therapy (n=296). According to the study, mortality in the testosterone-treated patients was reduced by an estimated 66-92%. [14]

The latest Endocrine Society clinical practice guidelines suggest testosterone therapy for men receiving high doses of glucocorticoids who also have low testosterone levels, to promote bone health. The guidelines also suggest such therapy in human immunodeficiency virus (HIV)infected men with low testosterone levels, to maintain lean bone mass and muscle strength.

See the article here:
Hypogonadism Treatment & Management: Approach ...

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By Anette Breindl Senior Science Editor

"With the advent of targeted cancer therapies, what we've found is that many of them are cardiotoxic," Saptarsi Haldar told BioWorld Today. "Pathways that are effective in cancer are toxic in the heart."

In the May 17, 2017, issue of Science Translational Medicine, Haldar, who is an associate investigator at the Gladstone Institute of Cardiovascular Disease, and his colleagues showed that a class of epigenetic drugs, the BET bromodomain inhibitors, may be not just an exception to that rule, but a class of drugs that has therapeutic utility in heart failure.

The team showed that the bromodomain inhibitor JQ-1 had therapeutic benefits in two separate animal models of advanced heart failure, but did not affect the beneficial changes to heart muscle cells that are a consequence of exercise.

The paper shows a potential new approach to heart failure an indication that, with a five-year survival rate of 60 percent, needs them.

It also shows a potential approach to another vexing problem, namely drugging transcription factors.

"There's a surprisingly tractable therapeutic index for drugging transcription in diseases," Haldar said.

While BRD4 is not itself a transcription factor, inhibiting it "dampens the transcription factor-driven network that's driving the disease . . . This is really about dampening transcriptional rewiring," he added.

In heart failure, those happen to be innate immune signaling and fibrotic signaling. Experiments in cardiac cells derived from induced pluripotent stem cells (iPSCs) showed that JQ-1 acted by blocking the activation of innate immune and profibrotic pathways, essentially preventing heart cells from rewiring themselves in maladaptive ways in response to being chronically overworked.

Haldar said the original idea to test whether the compound would have an effect in heart failure was based on "an educated guess."

Previous work had shown that certain epigenetic marks, namely acetyl marks on lysines, play a role in heart failure.

"There is a lot known about lysine acetylation in heart failure," Haldar said, and there had been previous attempts at targeting the process, which had "fallen to the wayside, in part because of issues with therapeutic index."

Even studying the molecular details of lysine acetylation's role in heart failure was challenging, because genetic approaches are not viable.

The problem became tractable with the synthesis of JQ-1 in the laboratory of James Bradner, who is a co-author on the Science Translational Medicine paper. The compound, which has been used to gain insight into epigenetic aspects of a large number of biological processes thanks to the decision of its developers to distribute it freely, targets BRD4, a "reader" protein that recognizes acetylated lysines. (See BioWorld Insight, Aug. 12, 2013.)

With the advent of JQ-1, Haldar said, "we immediately made the connection that here's a target BRD4 that you could specifically modulate that is recognizing acetyl-lysines on chromatin."

The team initially published work in 2013 showing that JQ-1 affected cellular processes in heart failure, and was an effective therapeutic in mice when given very early in the disease.

Patients, though, don't show up in their doctor's office very early in the disease. They show up with "pre-existing, often chronic heart failure," Haldar said.

At that point, the heart has already undergone significant remodeling that includes fibrosis and an activation of innate immune pathways.

The work now published in Science Translational Medicine showed that JQ-1 had effects even when given to mice that had established heart failure either due to a heart attack, or pressure overload, but did not block exercise-induced remodeling.

The team is hoping to test JQ-1 derivatives in large animal models, and ultimately take them into the clinic. Haldar is a co-founder of Tenaya Therapeutics Inc., a company launched in December with a $50 million series A financing from The Column Group. Haldar said that while he holds a patent on BET protein inhibition in heart disease, BET proteins are only "one of many targets/pathways that Tenaya is considering."

See the rest here:
Cancer drug class has cardiac benefits - BioWorld Online

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New research has nudged scientists closer to one of regenerative medicines holy grails: the ability to create customized human stem cells capable of forming blood that would be safe for patients.

Advances reported Wednesday in the journal Nature could not only give scientists a window on what goes wrong in such blood cancers as leukemia, lymphoma and myeloma. They could also improve the treatment of those cancers, which affect some 1.2 million Americans.

The stem cells that give rise to our blood are a mysterious wellspring of life. In principle, just one of these primitive cells can create much of a human beings immune system, not to mention the complex slurry of cells that courses through a persons arteries, veins and organs.

While the use of blood-making stem cells in medicine has been common since the 1950s, it remains pretty crude. After patients with blood cancers have undergone powerful radiation and chemotherapy treatments to kill their cancer cells, they often need a bone-marrow transplant to rebuild their white blood cells, which are destroyed by that treatment.

The blood-making stem cells that reside in a donors bone marrow and in umbilical cord blood that is sometimes harvested after a babys birth are called hematopoietic, and they can be life-saving. But even these stem cells can bear the distinctive immune system signatures of the person from whom they were harvested. As a result, they can provoke an attack if the transplant recipients body registers the cells as foreign.

This response, called graft-versus-host disease, affects as many as 70% of bone-marrow transplant recipients in the months following the treatment, and 40% develop a chronic version of the affliction later. It can overwhelm the benefit of a stem cell transplant. And it kills many patients.

Rather than hunt for a donor whos a perfect match for a patient in need of a transplant a process that can be lengthy, ethically fraught and ultimately unsuccessful doctors would like to use a patients own cells to engineer the hematopoietic stem cells.

The patients mature cells would be reprogrammed to their most primitive form: stem cells capable of becoming virtually any kind of human cell. Then factors in their environment would coax them to become the specific type of stem cells capable of giving rise to blood.

Once reintroduced into the patient, the cells would take up residence without prompting rejection and set up a lifelong factory of healthy new blood cells.

If the risk of deadly rejection episodes could be eliminated, physicians might also feel more confident treating blood diseases that are painful and difficult but not immediately deadly diseases such as sickle cell disease and immunological disorders with stem cell transplants.

The two studies published Wednesday demonstrate that scientists may soon be capable of pulling off the sequence of operations necessary for such treatments to move ahead.

One of two research teams, led by stem-cell pioneer Dr. George Q. Daley of Harvard Medical School and the Dana Farber Cancer Institute in Boston, started their experiment with human pluripotent stem cells primitive cells capable of becoming virtually any type of mature cell in the body. Some of them were embryonic stem cells and others were induced pluripotent stem cells, or iPS cells, which are made by converting mature cells back to a flexible state.

The scientists then programmed those pluripotent stem cells to become endothelial cells, which line the inside of certain blood vessels. Past research had established that those cells are where blood-making stem cells are born.

Here, the process needed a nudge. Using suppositions gleaned from experiments with mice, Daley said his team confected a special sauce of proteins that sit on a cells DNA and program its function. When they incubated the endothelial cells in the sauce, they began producing hematopioetic stem cells in their earliest form.

Daleys team then transferred the resulting blood-making stem cells into the bone marrow of mice to see if they would take. In two out of five mice who got the most promising cell types, they did. Not only did the stem cells establish themselves, they continued to renew themselves while giving rise to a wide range of blood cells.

A second research team, led by researchers from Weill Cornell Medicines Ansary Stem Cell Institute in New York, achieved a similar result using stem cells from the blood-vessel lining of adult mice. After programming those cells to revert to a more primitive form, the scientists also incubated those stem cells in a concoction of specialized proteins.

When the team, led by Raphael Lis and Dr. Shahin Rafii, transferred the resulting stem cells back into the tissue lining the blood vessels of the mice from which they came, that graft also took. For at least 40 weeks after the incubated stem cells were returned to their mouse owners, the stem cells continued to regenerate themselves and give rise to many blood-cell types without provoking immune reactions.

In addition to making a workhorse treatment for blood cancers safer, the new advances may afford scientists a unique window on the mechanisms by which blood diseases take hold and progress, said Lee Greenberger, chief scientific officer for the Leukemia and Lymphoma Society.

From a research point of view you could now actually begin to model diseases, said Greenberger. If you were to take the cell thats defective and make it revert to a stem cell, you could effectively reproduce the disease and watch its progression from the earliest stages.

That, in turn, would make it easier to narrow the search for drugs that could disrupt that disease process early. And it would speed the process of discovering which genes are implicated in causing diseases. With gene-editing techniques such as CRISPR-Cas9, those offending genes could one day be snipped out of hematopoietic stem cells, then be returned to their owners to generate new lines of disease-free blood cells.

Read more:
Scientists get closer to making personalized blood cells by using patients' own stem cells - Los Angeles Times

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Welsh rockers The Alarm are using their shows to encourage fans to become bone marrow donors.

The band, who are set to play at the Electric Ballroom in London, on Saturday, have arranged for swabbing station to be set up at the venue.

It means fans will be able to join a bone marrow donor registry with a simple cheek swab.

Leader singer Mike Peters, who has battled cancer three times, co-founded the Love Hope Strength Foundation in 2007 with the aim to "save lives, one concert at a time".

It hosts donor drives at concerts and festivals around the world by encouraging music fans aged 18 to 55 to sign up to the International Bone Marrow Registry.

To date, more than 150,000 music fans have joined the registry, and more than 3,100 potentially-lifesaving matches for blood cancer patients.

Bone marrow is a soft tissue found in the middle of certain bones. It contains stem cells, which are the "building blocks" for other normal blood cells (like red cells, which carry oxygen, and white cells, which fight infection).

Some diseases, such as leukaemia, prevent people's bone marrow from working properly. And for certain patients, the only cure is to have a stem cell transplant from a healthy donor.

Peters, 58, from North Wales, was first diagnosed with Hodgkin lymphoma in 1995. He has also battled leukaemia twice.

He said: "It's humbling to see how many people have responded to the Get On The List campaign so far."

Blood cancer charity DKMS, which is the world's largest donor centre, has worked with the LHS Foundation since 2013.

Joe Hallett, senior donor recruitment manager at the charity, said: "Only one in three people with a blood cancer in the UK and in need of a life-saving blood stem cell transplant will be lucky enough to find a suitable match within their own family.

"Finding a match from a genetically similar person can offer the best treatment, a second chance of life."

Last updated Fri 19 May 2017

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Rock band encourages fans to become bone marrow donors - ITV.com - ITV News

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BENGLURU: Fateh Singh, a six-year-old thalassemia major patient from Amritsar, underwent a bone marrow transplant last May which gave him a new lease of life. A year later, the boy met his saviour, Naval Chaudhary, whose stem cells were used for the procedure. The child was diagnosed with the condition when he was one-and-a-half years old.

On Thursday, the donor and recipient met for the first time. Naval, 28, a professional living in Bengaluru, had registered with DATRI, an unrelated blood stem cell donors registry in 2015. He said: "I was very happy to hear I was a potential match for a patient. But then I was told the donation process had to be done through bone marrow harvesting. Initially, I was a tad hesitant but then I researched the procedure and was counselled by Dr Sunil Bhat, paediatric haemato-oncologist from Mazumdar Shaw Cancer Centre."

"I realized that saving a life is more important than the type of procedure I had to go through. So I decided to go ahead," he added.

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6-year-old thalassemia patient from Punjab meets his stem cell ... - Times of India

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Exercise can burn the fat found within bone marrow, according to new research. The work, conducted with mice, offers evidence that this process improves bone quality and increases the amount of bone in a matter of weeks.

The study, published in the Journal of Bone and Mineral Research, also suggests obese individualswho often have worse bone qualitymay derive even greater bone health benefits from exercising than their lean counterparts.

One of the main clinical implications of this research is that exercise is not just good, but amazing for bone health, says lead author Maya Styner, a physician and assistant professor of endocrinology and metabolism at the University of North Carolina at Chapel Hill. In just a very short period of time, we saw that running was building bone significantly in mice.

Although research in mice is not directly translatable to the human condition, the kinds of stem cells that produce bone and fat in mice are the same kind as those that produce bone and fat in humans.

In addition to its implications for obesity and bone health, Styner says the research also could help illuminate some of the factors behind bone degradation associated with conditions like diabetes, arthritis, anorexia, and the use of steroid medications.

I see a lot of patients with poor bone health, and I always talk to them about what a dramatic effect exercise can have on bones, regardless of what the cause of their bone condition is, says Styner. With obesity, it seems that you get even more bone formation from exercise. Our studies of bone biomechanics show that the quality and the strength of the bone is significantly increased with exercise and even more so in the obese exercisers.

Bone marrow coordinates the formation of bone and cartilage while simultaneously churning out blood cells, immune cells, and cancerous cells.

Marrow also produces fat, but the physiological role of bone marrow fat in the bodyand even whether it is beneficial or harmful for ones healthhas remained somewhat mysterious.

Generally, marrow fat has been thought to comprise a special fat reserve that is not used to fuel energy during exercise in the same way other fat stores are used throughout the body during exercise. The new study offers evidence to the contrary.

Styners work also offers fundamental insights on how marrow fat forms and the impact it has on bone health. Previous studies have suggested that a higher amount of marrow fat increases the risk of fractures and other problems.

Theres been intense interest in marrow fat because its highly associated with states of low bone density, but scientists still havent understood its physiologic purpose, says Styner. We know that exercise has a profound effect on fat elsewhere in the body, and we wanted to use exercise as a tool to understand the fat in the marrow.

The researchers performed their experiments in two groups of mice. One group was fed a normal diet (lean mice) and the other received a high-fat diet (obese mice) starting a month after birth. When they were four months old, half the mice in each group were given a running wheel to use whenever they liked for the next six weeks. Because mice like to run, the group with access to a wheel tended to spend a lot of time exercising.

The researchers analyzed the animals body composition, marrow fat, and bone quantity at various points. Predictably, the obese mice started with more fat cells and larger fat cells in their marrow. After exercising for six weeks, both obese and lean mice showed a significant reduction in the overall size of fat cells and the overall amount fat in the marrow. In these respects, the marrow fat of exercising obese mice looked virtually identical to the marrow fat of lean mice, even those that exercised.

Perhaps more surprising was the dramatic difference in the number of fat cells present in the marrow, which showed no change in lean mice but dropped by more than half in obese mice that exercised compared to obese mice that were sedentary. The tests also revealed that exercise improved the thickness of bone, and that this effect was particularly pronounced in obese mice.

According to Styner, all of this points to the conclusion that marrow fat can be burned off through exercise and that this process is good for bones.

Obesity appears to increase a fat depot in the bone, and this depot behaves very much like abdominal and other fat depots, says Styner. Exercise is able to reduce the size of this fat depot and burn it for fuel and at the same time build stronger, larger bones.

The research leaves a few lingering mysteries. A big one is figuring out the exact relationship between burning marrow fat and building better bone. It could be that when fat cells are burned during exercise, the marrow uses the released energy to make more bone. Or, because both fat and bone cells come from parent cells known as mesenchymal stem cells, it could be that exercise somehow stimulates these stem cells to churn out more bone cells and less fat cells.

More research will be needed to parse this out. What we can say is theres a lot of evidence suggesting that marrow fat is being used as fuel to make more bone, rather than there being an increase in the diversion of stem cells into bone, says Styner.

Coauthors of the study are from UNC and State University of New York, Stony Brook. The National Institutes of Health Funded this research.

Source: UNC-Chapel Hill

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Exercise can even burn off fat in bone marrow - Futurity: Research News

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Athlone mother's desperate search for bone marrow donor for son (3)

Raqeeb Palm was diagnosed with Aplastic Anaemia in October after his mother noticed unusual bruises on his body.

Three-year-old Raqeeb Palm was diagnosed with Aplastic Anaemia in October after his mother noticed unusual bruises on his body. Picture: Monique Mortlock/EWN.

CAPE TOWN A mother from Heideveld in Athlone is desperately trying to find a bone marrow donor for her three-year-old son.

Raqeeb Palm was diagnosed with Aplastic Anaemia in October after his mother noticed unusual bruises on his body.

The boy had to undergo various blood tests and two bone marrow biopsies over a two-month period, before being diagnosed with the rare disease which damages bone marrow and stem cells.

Zaida Palm says her outgoing child can no longer play outside or do many of the activities three-year-olds enjoy due to his severely weakened immune system.

Hes got practically no immune system. So going out, malls, play areas, doing fun things is on a stop. Because any germ, he gets admitted [to the hospital] for a cold, he needs to go to the hospital.

Palm says they have been unable to find a bone marrow donor in South Africa.

A transplant is her son's only chance of survival.

Her medical aid won't cover an investigation for international donors, which is why she's turned to online crowd-funding.

The hundred thousand on the Backabuddy [website] is just the start to the campaign.

Palm has also urged people to become bone marrow donors.

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Athlone mother's desperate search for bone marrow donor for son (3) - Eyewitness News

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Nation | May. 19, 2017

New and controversial potential fertility technology called in vitro gametogenesis has caused pushback from some critics.

WASHINGTON Within the next 10-20 years, a new and controversial potential fertility technology called in vitro gametogenesis (IVG) could make it possible to manipulate skin cells into creating a human baby.

However, this groundbreaking research has caused pushback from some critics, like Father Tadeusz Pacholczyk, director of education at the National Catholic Bioethics Center, who says IVG would turn procreation into a transaction.

IVG extends the faulty logic of IVF [in vitro fertilization] by introducing additional steps to the process of manipulating the origins of the human person, in order to satisfy the desires of customers and consumers, Father Pacholczyk told CNA in an email interview.

The technology also offers the possibility of introducing further fractures into parenthood, distancing children from their parents by multiplying the number of those involved in generating the child, so that three-parent embryos, or even more parents, may become involved, he continued.

IVG has been successfully tested by Japanese researchers on mice, which produced healthy babies derived from skin cells.

The process begins by taking the skin cells from the mouses tail and reprograming them to become induced pluripotent stem cells. These manipulated cells are able to grow into different kinds of cells and are then used to grow eggs and sperm, which are then fertilized in the lab. The resulting embryos are then implanted in a womb.

Although similar to in vitro fertilization, IVG eliminates the step of needing pre-existing egg and sperm and instead creates these gametes.

But many experts in the reproductive field are skeptical of potential outcomes and ethical compromises.

It gives me an unsettled feeling because we dont know what this could lead to, Paul Knoepfler, a stem-cell researcher at the University of California, Davis,told The New York Times.

Knoepfler noted that some of the potential repercussions of IVG could turn into cloning or designer babies. Other dangers could include the Brad Pitt scenario, in which celebritys skin cells retrieved from random places, like hotel rooms, could be used to create a baby.

Potentially anyones skin cells could be used to create a baby, even without their knowledge or consent.

Inan issue ofScience Translational Medicineearlier this year, a trio of academics a Harvard Law professor, the dean of Harvard Medical School and a medical science professor at Brown University wrote that IVG may raise the specter of embryo farming on a scale currently unimagined, which might exacerbate concerns about the devaluation of human life.

They added that refining the science of IVG to the point of clinical use will involve the generation and likely destruction of large numbers of embryos from stem cellderived gametes, and the process may exacerbate concerns regarding human enhancement.

Father Pacholczyk also pointed to further concerns, saying IVG disrupts the uniqueness of every individuals sex cells.

IVG raises additional concerns because of the way it manipulates human sex cells. Our sex cells, or gametes, are special cells. They uniquely identify us, Father Pacholczyk stated.

It is most unfortunate that overwhelming parental desires are being permitted to trump and distort the right order of transmitting human life, he continued.

Father Pacholczyk said that processes like IVG enable a consumerist mentality that holds that children are projects to be realized through commercial transactions and laboratory techniques of gamete manipulation.

The Catholic Church teaches that IVF and similar reproductive technologies are morally illicit for several reasons, including their separation of procreation from the conjugal act and the creation of embryos which are discarded.

Pope Francis recently spoke out against the destruction of human embryos, saying that no good result from research can justify the destruction of embryos.

Some branches of research use human embryos, inevitably causing their destruction. But we know that no ends, even noble in themselves such as a predicted utility for science, for other human beings or for society can justify the destruction of human embryos,the Holy Father said May 18.

Although IVG has proven successful in mice, human testing is likely years away.

However, Father Pacholczyk hopes that potential parents will come to realize that children should not be viewed as products that can be ordered or purchased by consumers, but seen as a gift.

Turning commercial laboratories to create children on our behalf is an unethical step in the direction of treating our offspring as objects to be planned and created in the pursuit of parental gratification, rather than gifts received from the Lord.

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Can Skin Cells Create a Baby? - National Catholic Register

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The new technique heals burns much faster and more effectively than traditional skin grafting.

Burn victims may no longer be forced to undergo painful skin grafts, thanks to a revolutionary piece of technology that uses adult stem cells.

Instead of taking skin from one part of the body and transplanting it onto the burned area, a stem-cell spraying device simply covers the affected area with the victims own stem cells.

By taking adult stem cells from a healthy section of skin, placing them in a solution, and spraying the solution onto the wound, the patients own skin grows back and heals naturally.

The procedure has been in development for some time, and is not yet commercially available, but its capability was publicised in the press earlier this month.

The technology was featured in the Journal of the International Society for Burn Injuries, and showed incredible before and after images of the horrific injuries, and the victims almost full recoveries.

Patients who have benefitted from early treatments say their new skin is virtually indistinguishable from the rest of their body.

Commenting on the journals research, Thomas Bold, CEO of RenovaCare a company developing this technology said, the skin that regrows looks, feels and functions like the original skin.

By using adult stem cells, the healing process of the victims was also vastly accelerated.

While a skin graft treatment can take weeks or even months, and leave scarring, these patients were able to grow healthy skin in as little as four days.

In one case, a man who had suffered electrical burns to over a third of his body after touching a live wire had 24 million adult stem cells harvested and then sprayed back onto his body.

The process itself lasted only 90 minutes, and within four days, he had regrown a thin layer of skin over his arms and chest, where the burns were least severe.

After 20 days, all of the areas treated by the stem cell grafting process were described as completely healed.

RenovaCare is applying for a licence to use the technology in routine practice in Europe.

In January, it was revealed that a new technique allowed adult stem cells to be used in the treatment of heart problems.

The technique involves implanting synthetic cardiac stem cells which repair heart muscle. It has been praised as both an ethical and less risky alternative to other treatments.

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renovacareinc.com - The Christian Institute

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The Hindu

Babies from skin cells? Advance unsettles experts The Hindu It gives me an unsettled feeling because we don't know what this could lead to, said Paul Knoepfler, a stem cell researcher at the University of California, Davis. You can imagine one man providing both the eggs and the sperm, almost like cloning ...

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After two decades of research, scientists are on the cusp of entering a new era in stem-cell research that may transform the landscape of genetics and disease therapy.

In a first-ever clinical trial, researchers from Harvard University have created blood-forming stem cells, which they hope can one day serve to ameliorate genetic blood disorders and other conditions.

Were tantalizingly close to generating bona fide human blood stem cells in a dish, said senior investigator George Q. Daley, Dean of Harvard Medical School and head of a research lab in the Stem Cell Program at Boston Childrens Hospital. This work is the culmination of over 20 years of striving.

While scientists first isolated embryonic stem cells in 1998, they have found little success in the years since in using them to create legitimate blood-forming stem cells.

However, Daley tapped into years of work that had been done previously, including his teams creation of the first induced pluripotent stem (iPS) cells in 2007. While the team previously was able to use the iPS cells to produce other kinds of human cells, including brain and heart cells, they had no luck in their pursuit of blood-forming cells.

Related:Arthritis Vaccine Could Emerge From Stem Cell Technology

That is, until now. And the breakthrough puts them on pace to make a tremendous impact on patients with genetic disease, according to the study authors.

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, said study author Ryohichi Sugimura, a postdoctoral fellow in the Daley lab.

Currently, the approach of the Harvard researchers includes using viruses to alter the genetic material within the blood-forming cells that they have created. But their ultimate goal is to expand their ability to make true blood stem cells in a way thats practice[sp] and safe, without the need for viruses to signal genetic change.

Their new research may have cleared one long-standing barrier in the way of that realization.

Its proved challenging to see these cells, said Sugimura. You can roughly characterize blood stem cells based on surface markers, but even with this, it may not be a true blood stem cell. And once it starts to differentiate and make blood cells, you cant go back and study it its already gone.

Related:Scientists Grow Beating Heart Cells on Spinach Leaves

A better characterization of human blood stem cells and a better understanding of how they develop would give us clues to making bona fide human blood stem cells, added Sugimura.

To test the potency of their new approach, the Harvard team transplanted blood-forming cells into mice. After several weeks, some of the mice carried multiple types of human blood cells in their bone marrow and circulating blood, which means that the cells were actively working to create new blood cells within the animals bodies.

Were now able to model human blood function in so-called humanized mice, said Daley. This is a major step forward for our ability to investigate genetic blood disease.

The study appears online in the journal Nature.

A professional journalist nearly 30 years, David Heitz started his career at the Quad-City Times in Davenport, Iowa before moving to Los Angeles. He led the Glendale News-Press to best small daily newspaper in the state (CNPA) as managing editor and also worked as executive news editor of the Press-Telegram. He worked briefly as deputy news editor of the Detroit News before returning to the Quad-Cities, where he has worked as a freelance medical writer since 2012 for several national websites. He recently purchased his childhood home and says he truly is living the dream.

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Researchers Get Closer to First Lab-Grown Blood Stem Cells - Vital Updates

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From their giant fruits to compact plant size, todays tomatoes have been sculpted by thousands of years of breeding. But mutations linked to prized traitsincluding one that made them easier to harvestyield an undesirable plant when combined, geneticists have found.

It is a rare example of a gene harnessed during domestication that later hampered crop improvement efforts, says geneticist Zachary Lippman of Cold Spring Harbor Laboratory in New York. After identifying the mutations, he and his colleagues used CRISPR gene editing to engineer more productive plantsa strategy that plant breeders are eager to adopt.

Its pretty exciting, says Rod Wing, a plant geneticist at the University of Arizona in Tucson. The approach can be applied to crop improvement, not just in tomato, but in all crops.

Lippman knows his way around a tomato farm. As a teenager, he spent his summers picking the fruit by handa chore he hated. Rotten tomatoes. The smell lasts all day long, he says. I would always pray for rain on tomato-harvest day.

But years later, his interest in the genetics that control a plants shape led him back to tomato fields, to untangle the genetic changes that breeders had unknowingly made.

In the 1950s, researchers found a new trait in a wild tomato relative growing in the Galpagos Islands: it lacked the swollen part of the stem called the joint.

Joints are weak regions of the stem that allow fruit to drop off the plant. Wild plants benefit from dropping fruit because it helps seed dispersal. But with the advent of mechanical tomato pickers, farmers wanted their fruit to stay on the plant. Breeders rushed to incorporate the jointless trait into their tomatoes.

This new trait came with a downside. When it was crossed into existing tomato breeds, the resulting plants had flower-bearing branches that produced many extra branches and looked like a broom, terminating in a host of flowers. The flowers were a drain on plant resources, diminishing the number of fruits it produced. Breeders selected for other genetic variants that overrode this defect. But decades later, Lippman's team went looking for the genes behind this phenomenon.

They had previously screened a collection of 4,193 varieties of tomato, looking for those with unusual branching patterns. From that collection, they tracked down variants of two genes that, together, caused extreme branching similar to what plant breeders had seen. One of the two genes, the team reports in a paper published online inCellon 18 May, is responsible for the jointless trait.

The other gene favours the formation of a large green cap of leaf-like structures on top of the fruita trait that was selected for thousands of years ago, in the early days of tomato domestication. The benefits of this trait are unclear, Lippman says, but it may have helped to support heavier fruits.

With these genes uncovered, his team used CRISPRCas9 editing to eliminate their activity, as well as that of a third gene that also affects flower number, in various combinations. This generated a range of plant architectures, from long, spindly flower-bearing branches to bushy, cauliflower-like bunches of flowersincluding some with improved yields.

The findings should help to quell lingering doubts among plant breeders that negative interactions between desirable genetic traits are a force to be reckoned with, says Andrew Paterson, a plant breeder at the University of Georgia in Athens. The idea has been controversial, he says, because the effects have been difficult to detect statistically.

Lippmans team is now working with plant breeders to use gene editing to develop tomatoes with branches and flowers optimized for the size of the fruit. Plants with larger fruit, for example, may have better yields if they have fewer flowering branches than those with smaller fruit.

We really are tapping into basic knowledge and applying it to agriculture, he says. And ironically, it happens to be in the crop that I least liked harvesting on the farm.

This article is reproduced with permission and wasfirst publishedon May 18, 2017.

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Fixing the Tomato: CRISPR Edits Correct Plant-Breeding Snafu ... - Scientific American

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Precision editing DNA allows for some amazing applications.

Theres a revolution happening in biology, and its name is CRISPR.

CRISPR (pronounced crisper) is a powerful technique for editing DNA. It has received an enormous amount of attention in the scientific and popular press, largely based on the promise of what this powerful gene editing technology will someday do.

CRISPR was Science magazines 2015 Breakthrough of the Year; its been featured prominently in the New Yorker more than once; and The Hollywood Reporter revealed that Jennifer Lopez will be the executive producer on an upcoming CRISPR-themed NBC bio-crime drama. Not bad for a molecular biology laboratory technique.

CRISPR is not the first molecular tool designed to edit DNA, but it gained its fame because it solves some longstanding problems in the field. First, it is highly specific. When properly set up, the molecular scissors that make up the CRISPR system will snip target DNA only where you want them to. It is also incredibly cheap. Unlike previous gene editing systems which could cost thousands of dollars, a relative novice can purchase a CRISPR toolkit for less than US$50.

Research labs around the world are in the process of turning the hype surrounding the CRISPR technique into real results. Addgene, a nonprofit supplier of scientific reagents, has shipped tens of thousands of CRISPR toolkits to researchers in more than 80 countries, and the scientific literature is now packed with thousands of CRISPR-related publications.

When you give scientists access to powerful tools, they can produce some pretty amazing results.

The most promising (and obvious) applications of gene editing are in medicine. As we learn more about the molecular underpinnings of various diseases, stunning progress has been made in correcting genetic diseases in the laboratory just over the past few years.

Take, for example, muscular dystrophy a complex and devastating family of diseases characterized by the breakdown of a molecular component of muscle called dystrophin. For some types of muscular dystrophy, the cause of the breakdown is understood at the DNA level.

In 2014, researchers at the University of Texas showed that CRISPR could correct mutations associated with muscular dystrophy in isolated fertilized mouse eggs which, after being reimplanted, then grew into healthy mice. By February of this year, a team here at the University of Washington published results of a CRISPR-based gene replacement therapy which largely repaired the effects of Duchenne muscular dystrophy in adult mice. These mice showed significantly improved muscle strength approaching normal levels four months after receiving treatment.

Using CRISPR to correct disease-causing genetic mutations is certainly not a panacea. For starters, many diseases have causes outside the letters of our DNA. And even for diseases that are genetically encoded, making sense of the six billion DNA letters that comprise the human genome is no small task. But here CRISPR is again advancing science; by adding or removing new mutations or even turning whole genes on or off scientists are beginning to probe the basic code of life like never before.

CRISPR is already showing health applications beyond editing the DNA in our cells. A large team out of Harvard and MIT just debuted a CRISPR-based technology that enables precise detection of pathogens like Zika and dengue virus at extremely low cost an estimated $0.61 per sample.

Using their system, the molecular components of CRISPR are dried up and smeared onto a strip of paper. Samples of bodily fluid (blood serum, urine or saliva) can be applied to these strips in the field and, because they linked CRISPR components to fluorescent particles, the amount of a specific virus in the sample can be quantified based on a visual readout. A sample that glows bright green could indicate a life-threatening dengue virus infection, for instance. The technology can also distinguish between bacterial species (useful for diagnosing infection) and could even determine mutations specific to an individual patients cancer (useful for personalized medicine).

Almost all of CRISPRs advances in improving human health remain in an early, experimental phase. We may not have to wait long to see this technology make its way into actual, living people though; the CEO of the biotech company Editas has announced plans to file paperwork with the Food and Drug Administration for an investigational new drug (a necessary legal step before beginning clinical trials) later this year. The company intends to use CRISPR to correct mutations in a gene associated with the most common cause of inherited childhood blindness.

Physicians and medical researchers are not the only ones interested in making precise changes to DNA. In 2013, agricultural biotechnologists demonstrated that genes in rice and other crops could be modified using CRISPR for instance, to silence a gene associated with susceptibility to bacterial blight. Less than a year later, a different group showed that CRISPR also worked in pigs. In this case, researchers sought to modify a gene related to blood coagulation, as leftover blood can promote bacterial growth in meat.

You wont find CRISPR-modified food in your local grocery store just yet. As with medical applications, agricultural gene editing breakthroughs achieved in the laboratory take time to mature into commercially viable products, which must then be determined to be safe. Here again, though, CRISPR is changing things.

A common perception of what it means to genetically modify a crop involves swapping genes from one organism to another putting a fish gene into a tomato, for example. While this type of genetic modification known as transfection has actually been used, there are other ways to change DNA. CRISPR has the advantage of being much more programmable than previous gene editing technologies, meaning very specific changes can be made in just a few DNA letters.

This precision led Yinong Yang a plant biologist at Penn State to write a letter to the USDA in 2015 seeking clarification on a current research project. He was in the process of modifying an edible white mushroom so it would brown less on the shelf. This could be accomplished, he discovered, by turning down the volume of just one gene.

Yang was doing this work using CRISPR, and because his process did not introduce any foreign DNA into the mushrooms, he wanted to know if the product would be considered a regulated article by the Animal and Plant Health Inspection Service, a division of the U.S. Department of Agriculture tasked with regulating GMOs.

APHIS does not consider CRISPR/Cas9-edited white button mushrooms as described in your October 30, 2015 letter to be regulated, they replied.

Yangs mushrooms were not the first genetically modified crop deemed exempt from current USDA regulation, but they were the first made using CRISPR. The heightened attention that CRISPR has brought to the gene editing field is forcing policymakers in the U.S. and abroad to update some of their thinking around what it means to genetically modify food.

One particularly controversial application of this powerful gene editing technology is the possibility of driving certain species to extinction such as the most lethal animal on Earth, the malaria-causing Anopheles gambiae mosquito. This is, as far as scientists can tell, actually possible, and some serious players like the Bill and Melinda Gates Foundation are already investing in the project. (The BMGF funds The Conversation Africa.)

Most CRISPR applications are not nearly as ethically fraught. Here at the University of Washington, CRISPR is helping researchers understand how embryonic stem cells mature, how DNA can be spatially reorganized inside living cells and why some frogs can regrow their spinal cords (an ability we humans do not share).

It is safe to say CRISPR is more than just hype. Centuries ago we were writing on clay tablets in this century we will write the stuff of life.

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Beyond just promise, CRISPR is delivering in the lab today - The Conversation US

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What is CRISPR-Cas9?

CRISPR-Cas9 is a genome editing tool thats able to cut DNA in a targeted fashion, allowing scientists to accurately edit the building blocks of life.

It was actually first observed in the 1980s as part of single-celled bacterias defence mechanisms, which ensure that the cells are able to remove unwanted intruders. Scientists have found that, by adapting the technology, they are able to target genome sequences with unprecedented speed, precision and accuracy.

Picture CRISPR-Cas9 as like a find and replace search in a computer document, only instead of words, youre editing genetic sequences.

Accurately modifying DNA is a scientific holy grail, and the potential is enormous. It could be used to eradicate diseases even hereditary ones such as cystic fibrosis, sickle-cell anemia and Huntington's could become a thing of the past.

The name CRISPR is an acronym for the less catchy clustered regularly interspaced short palindromic repeats. The Cas part refers to CRISPR associated.

CRISPR is part of certain bacterias naturally occurring defences. When a bacteria detects an invading virus, it is able to copy and blend segments of the foreign DNA into its own genome around CRISPR.

The next time the virus is spotted, CRISPR has an exact copy of the genome sequence to look out for, which is where the Cas protein comes in: it can cut the DNA up, and disable unwanted genes with incredible accuracy.

Or, as Carl Zimmer explains: As the CRISPR region fills with virus DNA, it becomes a molecular most-wanted gallery, representing the enemies the microbe has encountered. The microbe can then use this viral DNA to turn Cas enzymes into precision-guided weapons. The microbe copies the genetic material in each spacer into an RNA molecule. Cas enzymes then take up one of the RNA molecules and cradle it. Together, the viral RNA and the Cas enzymes drift through the cell. If they encounter genetic material from a virus that matches the CRISPR RNA, the RNA latches on tightly. The Cas enzymes then chop the DNA in two, preventing the virus from replicating.

In 2012, scientists from the University of California, Berkeley, published a groundbreaking paper showing they were able to reprogramme the CRISPR-Cas immune system to edit genes at will. CRISPR-Cas9 uses a specific Cas protein and a hybrid RNA that can identify and edit any gene sequence. The possibilities are huge.

In short, CRISPR lists the DNA sequences to target, and then Cas9 does the cutting. Scientists just need to programme CRISPR with the right code, and Cas9 does the rest.

This could also apply to faulty genes sections currently causing problems could be removed with CRISPR-Cas9, and then replaced with healthy genetic code, theoretically solving the problem.

CRISPR is cutting edge technology, but while its true that its use has massively accelerated in recent years thanks to the above discovery, scientists have actually been aware of it in bacteria since the 1980s. Pubmed lists 5,775 papers discussing CRISPR but 5,575 of those have been in the three years since the UC Berkeley paper, and the number has jumped from 2,071 when I first wrote this article back in October 2015.

CRISPR-Cas9 isnt the first genomic editor, but it has a number of upsides that make it both simpler and far more efficient.

Firstly, CRISPR-Cas9 can edit multiple genes at once, whereas other genome editors such as zinc finger nuclease (ZFN) or transcription activator-like effector nucleases (TALENs) require painstaking modification of a single gene at a time. Its also quicker and cheaper, as you might expect.

Although ZFN and TALENs can recognise longer gene sequences than CRISPR-Cas9, custom proteins have to be created each time and its an inexact science, involving the creation of several variants before the winning combination is found.

On top of that, scientists tend to use ZFN and TALENs with organisms scientists know extremely well such as mice, rats and fruit flies. CRISPR-Cas9 should work with every organism ever evolved. Yes, including humans.

Yes, in China. Using human embryos sourced from a fertility clinic, scientists tried to use CRISPR-Cas9 to edit a gene that causes beta thalassemia in every cell. It should be noted that the donor embryos used were non-viable, and could not have resulted in a live birth.

In any case, it failed, and failed quite badly: 86 embryos were injected, and after 48 hours and around eight cells grown, 71 survived, and 54 of those were genetically tested. Just 28 had been successfully spliced, and very few contained the genetic material the researchers intended. If you want to do it in normal embryos, you need to be close to 100%, lead researcher Jungiu Huang told Nature. Thats why we stopped. We still think its too immature.

On top of that, its extremely likely more undocumented damage was done. As the New York Times explains: The Chinese researchers point out that in their experiment gene editing almost certainly caused more extensive damage than they documented; they did not examine the entire genomes of the embryo cells.

As you might imagine, it caused a huge amount of controversy in the scientific community.

In November 2016, another grouip of Chinese scientists became the first to use CRISPR-Cas9 on an adult human, injecting a lung cancer sufferer with the patient's immune cells modified by CRISPR to disable the PD-1 protein, theoretically making the patient's body fight back against the cancer. Results are still yet to be reported. The first American trial of CRISPR in humans is due to take place at the University of Pennsylvania later this year again with cancer.

Even though the Chinese scientists used embryos that were not going to develop into life, there are real ethical concerns about experimenting on human embryos indeed, just a month before the Chinese research was published, a group of American scientists urged the world not to do so.

Part of this comes down to how immature the technology is remember that its only been in active use since 2012, and it would be astonishing if it was fully matured at this point. Scientists warned that it was too misunderstood and dangerous to use on humans at this point, and the Chinese research certainly vindicates this concern. Even if it worked flawlessly, there are concerns that unforeseen consequences could occur over generations.

But, even if it were 100% safe and successful, there are other ethical concerns: while nobody argues that we should hold back the potential of wiping out killer genetic diseases such as Huntingtons and cystic fibrosis, CRISPR-Cas9 potentially offers the opportunity to change anything about a person. As long as the genetic sequence is identified, in theory, it can be edited.

Its one thing to remove life-impacting diseases before birth its quite another for parents to be able to design their babies to be stronger, faster or better looking. Even if you accept that this is something people should be allowed to do, the chances are this would be heavily commercialised, ensuring only the rich could afford all the extra life advantages this would afford, massively affecting inequality.

Of course, these ethical questions are a million miles away when the only recorded embryonic human experiment was such a high-profile set-back. However, CRISPR-Cas9 is now showing extremely promising results in smaller tests.

Examples include HIV infection prevention in human cells, curing genetic mouse diseases and a pair of monkeys born with targeted mutations. As Wired says, it "kills HIV and eats Zika like Pac-man," with hopes that cancer could be the next disease in its sights.

Yes. Stem cell researchers in the UK sought permission to modify human embryos in an attempt to understand early human development, and reduce the likelihood of miscarriage. In February 2016, theHuman Fertilisation and Embryology Authority (HFEA) granted permission.

As mentioned previously, Cas9 can only recognise genetic sequences of around 20 bases long, meaning that longer sequences cannot be targeted.

More significantly, the enzyme still sometimes cuts in the wrong place. Figuring out why this is will be a significant breakthrough in itself fixing it will be even bigger.

Then, of course, theres the issue that CRISPR didnt work terribly well in human embryos. Scientists need to discover what went wrong there, and what the difference is between the success in single cells and the more patchy results with embryos.

That isnt a simple question to answer. Its subject to an ongoing patent battle surprisingly, given CRISPR is naturally occurring in certain bacteria.

Technology Review explains that, although CRISPR-Cas9 was first described in Science in 2012 by Jennifer Doudna from UC Berkeley, Feng Zhang from the Broad Institute won a patent on the technique by submitting lab notebooks proving hed invented it first.

First to file patent rights means that this should be granted to Doudna, but the decision could have been decided based on first to invent rules, which would have favoured Zhang. In the end, the case was resolved in February 2017, when the US Patent Trial and Appeal Board resolved that UC Berkeley would be granted the patent for the use of CRISPR-Cas9 in any living cell, while Broad would get it in any eukaryotic cell which is to say cells in plants and animals.

Images: Petra B Fritz, VeeDunn, NIH Image Gallery, and Steve Jurvetson used under Creative Commons

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What is CRISPR-Cas9, and will it change the world? | Alphr - Alphr

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