Archive for the ‘Skin Stem Cells’ Category

Newswise Irvine, Calif., April 24, 2017 Using human skin cells, University of California, Irvine neurobiologists and their colleagues have created a method to generate one of the principle cell types of the brain called microglia, which play a key role in preserving the function of neural networks and responding to injury and disease.

The finding marks an important step in the use of induced pluripotent stem (iPS) cells for targeted approaches to better understand and potentially treat neurological diseases such as Alzheimers. These iPS cells are derived from existing adult skin cells and show increasing utility as a promising approach for studying human disease and developing new therapies.

Skin cells were donated from patients at the UCI Alzheimers Disease Research Center. The study, led by Edsel Abud, Wayne Poon and Mathew Blurton Jones of UCI, used a genetic process to reprogram these cells into a pluripotent state capable of developing into any type of cell or tissue of the body.

The researchers then guided these pluripotent cells to a new state by exposing the cells to a series of differentiation factors which mimicked the developmental origin of microglia. The resulting cells act very much like human microglial cells. Their study appears in the current issue of Neuron. Link: http://www.cell.com/neuron/fulltext/S0896-6273(17)30286-6.

In the brain, microglia mediate inflammation and the removal of dead cells and debris. These cells make up 10- to 15-percent of brain cells and are needed for the development and maintenance of neural networks.

Microglia play an important role in Alzheimers and other diseases of the central nervous system. Recent research has revealed that newly discovered Alzheimers-risk genes influence microglia behavior. Using these cells, we can understand the biology of these genes and test potential new therapies, said Blurton-Jones, an assistant professor of the Department of Neurobiology & Behavior and Director of the ADRC iPS Core.

Scientists have had to rely on mouse microglia to study the immunology of AD. This discovery provides a powerful new approach to better model human disease and develop new therapies, added Poon, a UCI MIND associate researcher.

Along those lines, the researchers examined the genetic and physical interactions between Alzheimers disease pathology and iPS-microglia. They are now using these cells in three-dimensional brain models to understand how microglia interact with other brain cells and influence AD and the development of other neurological diseases.

Our findings provide a renewable and high-throughput method for understanding the role of inflammation in Alzheimers disease using human cells, said Abud, an M.D./Ph.D. student. These translational studies will better inform disease-modulating therapeutic strategies.

Blurton Jones, Abud and Poon are with UCIs Institute for Memory Impairments and Neurological Disorders (UCI MIND). Ricardo Ramirez, Eric Martinez, Cecilia Nguyen, Sean Newman, Vanessa Scarfone, Samuel E. Marsh, Cristhian Fimbres, Chad A. Caraway, Ali Mortazavi, Michael Cahalan, Brian Cummings, Gianna Fote, Andriy Yeromin and Anshu Agrawal with UCI; Luke Healy and Jack Antel with McGill University, Montreal; Rakez Kayed with the University of Texas Medical Branch, Galveston, Texas; Karen Gylys with UCLA; and Abdullah Madany and Monica Carson with UC Riverside contributed to the study. The National Institutes of Health, the California Institute for Regenerative Medicine, and the Susan Scott Foundation provided support.

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Skin Stem Cells Used to Generate New Brain Cells - Newswise (press release)

Stem cells help researchers identify neuronal defects causing ... Science Daily Researchers have used stem cells derived from patients with Angelman syndrome to identify the underlying neuronal defects that cause the rare neurogenetic ... and more »

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Stem cells help researchers identify neuronal defects causing ... - Science Daily

An international group of scientists led by investigators at the Technical University of Munich (TUM) says it has discovered molecular mechanisms that might prevent the development ofgraft-versus-host disease (GVHD) in individuals receiving stem cell transplants.

During GVHD, transplanted stem cells become T lymphocytes, which are supposed to fight intruders such as bacteria. Instead, they start attacking the recipients already weakened body.

Researchers from TUM and theMemorial Sloan Kettering Cancer Center published a study ("RIG-I/MAVS and STING Signaling Promote Gut Integrity during Irradiation- and Immune-Mediated Tissue Injury")in Science Translational Medicine that provides details on how to prevent the development of GVHD.

The attacks by the T cells primarily affect the skin, liver, and, in particular, the gastrointestinal tract. The intestine is believed to be the key organ where GVHD starts. The drug treatment and radiation involved in stem cell transplants damage epithelial cells, which form part of the intestinal mucosal layer. Stress signals emitted by the dying epithelial cells and the arrival of intestinal bacteria in the previously germ-free areas of the gut due to the loss of the epithelium trigger the activation of aggressive donor T cells.

"If the epithelium could be protected or quickly restored, the risk of an immune response would be much lower," says Hendrik Poeck, M.D., Ph.D., who, along with Tobias Haas, M.D., heads a research group at the third medical clinic of TUM's Klinikum rechts der Isar. "Up to now, however, there have been very few treatment strategies that seek to regenerate the epithelium."

The scientists working with Dr. Poeck studied two proteins produced naturally in the body and known for their role in fighting bacteria and viruses: RIG-I (retinoic acid-inducible gene I) and STING (stimulator of interferon genes). "We were able to demonstrate for the first time that both of them can also be used to bring about a regenerative effect," notes Julius Fischer, first author of the study.

Both proteins are part of signal chains that cause type I interferon (IFN-I) to be produced. IFN-I triggers many different immune responses, but can also speed up the replacement of epithelial cells.

The RIG-I signal pathway can be deliberately stimulated using triphosphate-RNA (3pRNA). Poeck and his team were able to demonstrate in mice that 3pRNA can indeed protect the epithelial cells. Timing is critical. Measurable protection was only seen when the 3pRNA was administered exactly 1 day before the start of radiation and drug treatment.

"We assume that after just 1 day of treatment, there would no longer be enough intact epithelial cells in the gut for the RIG-I/IFN signal path to function," explains Haas. Although fewer activated T cells were generated after a treatment with 3pRNA, the positive effect of the leukemia therapy was not reduced to a measurable degree.

Both RIG-I agonists, such as 3pRNA, and STING agonists are currently in clinical development. The research points to a wide range of potential applications, especially in the treatment of tumors.

"Our study shows that regenerative processes can also be triggered through selective activation of these signal paths," adds Poeck. "It thus appears quite possible that these selective agonists will be administered in the future to patients who are candidates for allogeneic stem cell transplants. However, further studies will be needed to learn how they actually work before applications in human medicine are possible."

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Preventing Graft-Versus-Host Disease in Stem Cell Transplant Recipients - Genetic Engineering & Biotechnology News (press release)

The New Cellogica Website Features In-Depth Information about the Skin Care Product, which Includes Stem Cell Technology

LOS ANGELES, CA / ACCESSWIRE / April 20, 2017 / The founders of Cellogica, a top line of skincare products that utilize stem cells and other innovative ingredients, are pleased to announce the re-launch of their website, Cellogica.com.

To check out the recently revised website, which is now easier than ever to navigate and features updated information about Cellogica, please visit http://www.cellogica.com at any time.

As a company spokesperson noted, Cellogica's "Two Secrets of Youth" involve the use of stem cell technology and also its MAC-5 Complex, which includes five ingredients that may help the skin look as young as possible. Rather than merely repairing the skin, Cellogica may actually help stop the loss of existing skin stem cells, as well as prevent premature aging.

Cellogica features a day cream, a non-greasy and light product which is designed to protect and enhance the skin and provide it with a natural barrier to the damaging UV rays of the sun and harsh weather. It also includes a night cream that works as the user sleeps by naturally repairing, restoring and regenerating the skin.

As the spokesperson noted, because skin stem cells are responsible for regenerating new and healthy skin cells, the founders of Cellogica were inspired to create a skin care cream that contains stem cells.

"Our revolutionary Stem Cell Technology is derived from strains of rare Swiss apples (Malus Domestica) and the Alpine Rose (Rhododentron Ferrugineum)," the spokesperson said, adding that together, these two very powerful stem cell extracts may allow for the regeneration of new skin stem cells, prevent the loss of existing skin stem cells, and increase the skin's barrier function.

"They may protect and repair the skin and combat against chronological aging, thus leading to fresh, healthy and vibrant looking skin."

The MAC-5 Complex is the other key component to Cellogica's ability to help improve the appearance of the skin. The proprietary combination includes Syn-Coll, which is an aqueous unpreserved glycerin-based solution that was developed to reduce wrinkles, as well as stimulate collagen synthesis. The other four ingredients in the MAC-5 Complex are RonaFlair LDP, hyaluronic acid, Syn-Ake, and Kojic acid, which may help eliminate blotchy skin while evening out the skin tone.

About Cellogica:

Cellogica is a premiere skincare line utilizing newly discovered stem cells to stop and reverse the physical signs of aging. To learn more about the product, please visit their website, http://www.cellogica.com.

Contact:

Darryl Burke admin@rocketfactor.com (949) 555-2861

SOURCE: Power Americas Minerals Corp.

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Cellogica Launches Their Updated and More User-Friendly Website, Cellogica.com - Yahoo Finance

Technology Networks

Brain Organoid Created from Stem Cells | Technology Networks Technology Networks Technology Networks is an internationally recognised publisher that provides access to the latest scientific news, products, research, videos and posters. and more »

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Brain Organoid Created from Stem Cells | Technology Networks - Technology Networks

Salk scientists and collaborators have shed light on a long-standing question about what leads to variation in stem cells by comparing induced pluripotent stem cells (iPSCs) derived from identical twins. Even iPSCs made from the cells of twins, they found, have important differences, suggesting that not all variation between iPSC lines is rooted in genetics, since the twins have identical genes.

Because they can differentiate into almost any cell type in the body, stem cells have the potential to be used to create healthy cells to treat a number of diseases. But stem cells come in two varieties: embryonic stem cells (ESCs), which are isolated from embryos, and iPSCs, which are created in the lab from adult cells that are reprogrammed using mixtures of signaling molecules and are a promising tool for understanding disease and developing new treatments.

Although iPSCs resemble ESCs in most ways, scientists have found that iPSCs often have variations in their epigenetics methyl marks on the DNA that dictate when genes are expressed. These epigenetic markers arent the same between iPSCs and ESCs, or even between different lines of iPSCs. In the past, its been hard to determine what drives these differences.

When we reprogram cells, we see small differences when we compare them to stem cells that come from an embryo. We wanted to understand what types of differences are always there, what is causing them, and what they mean, says Juan Carlos Izpisua Belmonte, a professor in Salks Gene Expression Laboratory and co-senior author, with Kelly Frazer of the University of California, San Diego, on the new paper, which was published in Cell Stem Cell in April 2017. A better understanding of these differences will help researchers refine stem-cell based treatments for disease.

Izpisua Belmonte and Frazer, along with co-first authors of the paper Athanasia Panopoulos, formerly a postdoctoral fellow at Salk and now at the University of Notre Dame, and Erin Smith of UCSD, turned to twins to help sort it out.

Although identical twins have the same genes as each other, their epigenomesthe collection of methyl marks studding their DNAare different by the time they reach adulthood due in part to environmental factors. Reprogramming the skin cells of adult identical twins to their embryonic state eliminated most of these differences, the researchers found when they studied cells from three sets of twins. However, there were still key epigenetic differences between twins in terms of how the iPSCs compared to ESCs.

When the team looked more in depth at the spots of the genome where this variation between methyl marks tended to show up in twins, they found that they often fell near binding sites for a regulatory protein called MYC.

In the past, researchers had found lots of sites with variations in methylation status, but it was hard to figure out which of those sites had variation due to genetics, says Panopoulos. Here, we could focus more specifically on the sites we know have nothing to do with genetics. That new focus, she says, is what allowed them to home in on the MYC binding sites.

The MYC proteinwhich is one of the molecules used to reprogram iPSCs from adult cellslikely plays a role in dictating which sites in the genome are randomly methylated during the reprogramming process, the researchers hypothesized.

The twins enabled us to ask questions we couldnt ask before, says Panopoulos. Youre able to see what happens when you reprogram cells with identical genomes but divergent epigenomes, and figure out what is happening because of genetics, and what is happening due to other mechanisms.

The findings help scientists better understand the processes involved in reprogramming cells and the differences between iPSCs and ESCs, which has implications on future studies aiming to understand the specific causes and consequences of these changes, and the way iPSCs are being used for research and therapeutics.

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Identical twins; not-so-identical stem cells - ScienceBlog.com - ScienceBlog.com (blog)

Third in an occasional series on how Harvard researchers are tackling the problematic issues of aging.

If only, wrote an ancient Japanese poet, when one heard that Old Age was coming one could bolt the door.

Science is working on it.

Aging is as much about the physical processes of repair and regeneration and their slow-motion failure as it is the passage of time. And scientists studying stem cell and regenerative biology are making progress understanding those processes, developing treatments for the many diseases whose risks increase as we get older, while at times seeming to draw close to a broader anti-aging breakthrough.

If stem cells offer potential solutions, theyre also part of the problem. Stem cells, which can differentiate into many cell types, are important parts of the bodys repair system, but lose regenerative potency as we age. In addition, their self-renewing ability allows the mutations that affect every cell to accumulate across cellular generations, and some of those mutations lead to disease.

We do think that stem cells are a key player in at least some of the manifestations of age, said Professor of Stem Cell and Regenerative Biology David Scadden, co-director of the Harvard Stem Cell Institute. The hypothesis is that stem cell function deteriorates with age, driving events we know occur with aging, like our limited ability to fully repair or regenerate healthy tissue following injury.

When it comes to aging, certain tissue types seem to lead the charge, according to Professor of Stem Cell and Regenerative Biology Lee Rubin, who directs the Harvard Stem Cell Institutes Therapeutic Screening Center. Particular tissues nerve cells appear to be one somehow signal to others that its time to age. This raises the prospect, Rubin said, that aging might be reversed by treating these key tissue categories, rather than designing individual treatments for the myriad tissue types that make up the body.

The process of aging involves all tissues in your body and, while different things go wrong in each tissue, they go wrong at basically the same rate, Rubin said. We can think of it as a process that is somehow coordinated, or there are fundamental processes in each tissue that play out.

In addition to key tissues, certain chemical pathways like insulin signaling seem to be able to control aging, said Rubin, whose work has received backing from the National Institute of Neurological Disorders and Stroke, as well as private foundations. The insulin signaling pathway is a chemical chain reaction in which the hormone insulin helps the body metabolize glucose. Reducing it has been shown to greatly extend life span in flies and worms, Rubin said. Also, signaling doesnt have to be reduced in all tissues.

If you just reduce it in neurons, the whole fly or worm lives longer, Rubin said. Certain key tissues in those organisms, if you selectively manipulate those tissues, have a positive effect on a number of processes in other tissues.

Because it circulates throughout the body, blood is an obvious place to look for controlling or signaling molecules that prompt or coordinate aging. A key carrier of oxygen and nutrients, blood is also rich with other compounds, some of which appear to play a role in decline linked to age.

Scadden described recent work done separately by Ben Ebert, a professor of medicine working at Harvard-affiliated Brigham and Womens Hospital, and Steve McCarroll, the Dorothy and Milton Flier Associate Professor of Biomedical Science and Genetics, that identified age-related changes in the blood that can increase the risk of diseases we dont typically think of as blood diseases.

Another tantalizing study, published in 2013, used the blood of a young mouse to rejuvenate the organs of an older one. In these parabiotic experiments, conducted by Professor of Stem Cell and Regenerative Biology Richard Lee and Forst Family Professor of Stem Cell and Regenerative Biology Amy Wagers, the circulatory systems of the two mice were joined, allowing the blood of the young to flow through the older ones body. The older mouse showed improvements in muscle tone and heart function. Later, similar experiments done by Rubin also showed improvements in neuronal health and brain functioning.

The young mouses fate depended on the age of the older mouse, Rubin said. If the latter was middle-aged, the young mouse appeared to be fine. If the older mouse was very old, however, the young mouse did worse.

Rubin said the experiments suggest that blood contains both positive and negative factors that influence aging. It may be, he said, that both are always present, but that positive factors outweigh negative in the young and that negative factors increase as we age.

Researchers have identified but not yet confirmed candidate blood factors for the rejuvenating effects. What seems not in doubt is the overall effect of the young blood on the old mouse. Interest is intense enough that a California company, Alkahest, has begun experiments giving Alzheimers patients plasma from young blood in hopes of improving cognition and brain function.

Even if that approach works, Rubin said, there would be practical hurdles to the widespread administration of young peoples blood plasma to older patients. But with an active compound identified, a drug could be made available to restore at least some cognitive function in Alzheimers patients.

In addition to the overall process of aging, researchers at the Harvard Stem Cell Institute, as well as across the University and its affiliated institutions, are investigating an array of diseases whose incidence increases sometimes dramatically with age.

The list includes several of the countrys top causes of death heart disease, stroke, diabetes, and cancer as well as rarer conditions such as the lethal neurodegenerative disorder amyotrophic lateral sclerosis (ALS).

Two decades ago, when stem cell research hit mainstream consciousness, many thought its greatest promise would be in stem cells ability to grow replacement parts: organs and tissues for damage caused by trauma or disease.

The stem cell revolution is still developing, Scadden said, but so far has taken a different form than many expected. The dream of harnessing stem cells to grow replacement hearts, livers, and kidneys remains, but potentially powerful uses have emerged in modeling disease for drug discovery and in targeting treatment for personalized medicine.

We thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

David Scadden

Researchers have taken from the sick easily accessible cells, such as skin or blood, and reprogrammed them into the affected tissue type nerve cells in the case of ALS, which most commonly strikes between 55 and 75, according to the National Institutes of Health (NIH).

These tissues are used as models to study the disease and test interventions. Work on ALS in the lab of Professor of Stem Cell and Regenerative Biology Kevin Eggan has identified a drug approved for epilepsy that might be effective against ALS. This application is now entering clinical trials, in collaboration with Harvard-affiliated Massachusetts General Hospital.

In the end, stem cells might have their greatest impact as a drug-discovery tool, Scadden said.

Much of stem cell medicine is ultimately going to be medicine, he said. Even here, we thought stem cells would provide mostly replacement parts. I think thats clearly changed very dramatically. Now we think of them as contributing to our ability to make disease models for drug discovery.

Also evolving is knowledge of stem cell biology. Our previous understanding was that once embryonic stem cells differentiated into stem cells for muscle, blood, skin, and other tissue, those stem cells remained flexible enough to further develop into an array of different cells within the tissue, whenever needed.

Recent work on blood stem cells, however, indicates that this plasticity within a particular tissue type may be more limited than previously thought, Scadden said. Instead of armies of similarly plastic stem cells, it appears there is diversity within populations, with different stem cells having different capabilities.

If thats the case, Scadden said, problems might arise in part from the loss of some of these stem cell subpopulations, a scenario that could explain individual variation in aging. Getting old may be something like the endgame in chess, he said, when players are down to just a few pieces that dictate their ability to defend and attack.

If were graced and happen to have a queen and couple of bishops, were doing OK, said Scadden, whose work is largely funded through the NIH. But if we are left with pawns, we may lose resilience as we age.

Scaddens lab is using fluorescent tags to mark stem cells in different laboratory animals and then following them to see which ones do what work. It might be possible to boost populations of particularly potent players the queens to fight disease.

Were just at the beginning of this, Scadden said. I think that our sense of stem cells as this highly adaptable cell type may or may not be true. What we observe when we look at a population may not be the case with individuals.

The replacement parts scenario for stem cells hasnt gone away. One example is in the work of Harvard Stem Cell Institute co-director and Xander University Professor Douglas Melton, who has made significant progress growing replacement insulin-producing beta cells for treatment of diabetes.

Another is in Lees research. With support from the NIH, Lee is working to make heart muscle cells that can be used to repair damaged hearts.

Trials in this area have already begun, though with cells not genetically matched to the patient. In France, researchers are placing partially differentiated embryonic stem cells on the outside of the heart as a temporary aid to healing. Another trial, planned by researchers in Seattle, would inject fully differentiated heart muscle cells into a patient after a heart attack as a kind of very localized heart transplant.

Lees approach will take longer to develop. He wants to exploit the potential of stem cell biology to grow cells that are genetically matched to the patient. Researchers would reprogram cells taken from the patient into heart cells and, as in the Seattle experiment, inject them into damaged parts of the heart. The advantage of Lees approach is that because the cells would be genetically identical to the patient, he or she could avoid antirejection drugs for life.

What were thinking about is longer-term but more ambitious, Lee said. Avoiding immune suppression could change the way we think about things, because it opens the door to many decades of potential benefit.

Change has been a constant in Lees career, and he says theres no reason to think that will slow. Patient populations are older and more complex, disease profiles are changing, and the tools physicians have at their disposal are more powerful and more targeted.

Many of our patients today wouldnt be alive if not for the benefit of research advances, he said. Cardiology has completely changed in the last 25 years. If you think its not going to change even more in the next 25 years, youre probably wrong.

When Lee envisions the full potential of stem cell science, he sees treatments and replacement organs with the power to transform how we develop and grow old.

It may not be there for you and me, but for our children or their children, ultimately, regenerative biology and stem cell biology have that kind of potential, he said. We imagine a world where it doesnt matter what mutations or other things youre born with, because we can give you a good life.

Lees not guessing at future longevity. Hes not even sure extending life span beyond the current record, 122, is possible. Instead, he cites surveys that suggest that most Americans target 90 as their expectation for a long, healthy life.

Thats about a decade more than we get now in America, Lee said. We have work to do.

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Researchers study secrets of aging via stem cells - Harvard Gazette

Medical Xpress

Protein primes mouse stem cells to quickly repair injury, study finds ... Science Daily Like drag car racers revving their engines at the starting line, stem cells respond more quickly to injury when they've been previously primed with one dose of a ... Alerting stem cells to hurry up and heal - Medical XpressMedical Xpress all 3 news articles »

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Protein primes mouse stem cells to quickly repair injury, study finds ... - Science Daily

BY: DUSTIN BATTY

Stem cell research is a controversial topic that is often vilified in the minds of the general public. This is in part because of the vast mainstream media coverage of the debates surrounding the use of embryonic stem cells, and their tendency to refer to the issue simply as the stem cell controversy rather than specifying that the problematic stem cells are those harvested from embryos.

Embryonic stem cells aside, though, there is still some discussion in bioethical circles about the harvesting of stem cells from bone marrow and even from skin. According to a study exploring an alternative method of obtaining stem cells, the debates surrounding the extraction of stem cells from even a mildly invasive procedure such as a skin biopsy are particularly relevant when one is procuring cells from vulnerable populations, such as children and individuals with intellectual disability. The study was undertaken to prove the viability of a non-invasive method of procuring stem cells from individuals with Down syndrome.

The method used by the researchers was surprisingly successful. They managed to extract cells from urine samples that were able to become induced pluripotent stem cells (iPSC), which means that the cells were altered so they could act like stem cells. Notably, the iPSCs obtained from the urine samples were superior to those harvested from skin biopsies and other methods because theyd had no exposure to ultraviolet light, and thus their DNA was generally undamaged.

Perhaps the most significant advantage that iPSCs from urine samples have over other methods is their completely non-invasive nature. This is particularly true when collecting stem cells from individuals with Down syndrome; in the past, a significant percentage of such individuals or their parents or guardians have refused to go forward with skin biopsies, limiting the availability of material for developing treatment methods. Research ethics boards have also been known to prevent the wide-scale use of skin biopsies in individuals with DS [Down syndrome]. This new method is expected to relieve the anxieties of the individuals involved, and should be easily accepted by ethics boards as well.

The researchers expect that the use of this method will improve both the quality of cells used and the quantity available to be studied. This increased availability is important to the efficient continuation of research into treatments for Down syndrome. Although such research begins with the use of lab mice to test the viability of new treatment methods, mouse physiology is so much simpler than that of humans that such tests arent sufficient. Eventually, the treatment needs to be tested on human cells. Stem cells are particularly useful for these kinds of tests because they are able to grow into a variety of different cells, which can be tested with the treatment individually.

The researchers conclude with the assurance that the techniques they implemented could be useful not only for research into Down syndrome, but also in the study of other neurodevelopmental and neurodegenerative disorders.

Providing better quality cells with increased participation and no ethical concerns, this new method of harvesting stem cells could be the answer that medical researchers were looking for.

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Stem cells can now be gathered from urine samples - The Plaid Zebra (blog)

Salk Institute and Chinese researchers report creating a new kind of stem cell, one that is more versatile than any other normally grown in the lab.

Called an extended pluripotent stem cell, it can give rise to every cell type in the body, the researchers say in a recent study. This includes the extra-embryonic tissues such as the placenta that support the developing baby. Just one cell can generate a complete organism.

Embryonic stem cells and artificial embryonic stem cells called induced pluripotent stem cells cant make these extra-embryonic tissues. So neither embryonic nor IPS cells can give rise to a complete embryo, because the supportive tissues necessary for an embryo to survive arent there.

But the extended pluripotent stem cells can reliably give rise to both types of cells, and thus whole embryos and offspring, the scientists report.

The EPS cells were made from human and mouse embryonic stem cells. In addition, they were produced from skin cells, or fibroblasts by treating them with a chemical cocktail. IPS cells, invented in 2006, are generated from fibroblasts by a similar reprogramming process.

To demonstrate this ability to make all cell types, the researchers grew an entire mouse from just one EPS cell. They also grew chimeric mice, with human EPS cells integrating into the mice better than embryonic stem cells did.

The study on these new stem cells was published April 6 in the journal Cell. It can be found at j.mp/extendedstem.

Better tool

That characteristic of creating every cell in the body, called totipotency, is normally found only at the very beginning of embryonic development. Embryonic stem cells are usually extracted too late, when the cells have already divided into the embryonic and extra-embryonic lineages.

Totipotent stem cells have been observed in the lab, but they lasted briefly, and didnt yield stable totipotent cell lines.

Salk Institute stem cell researcher Juan Carlos Izpisa Bemonte was a cosenior author of the paper along with Hongkui Deng of Peking University in Beijing. The first authors were Yang Yang, Bei Liu, Jun Xu, and Jinlin Wang; all of Peking University, and Jun Wu, of the Salk Institute.

EPS cell lines provide a useful cellular tool for gaining a better molecular understanding of initial cell fate commitments and generating new animal models to investigate basic questions concerning development of the placenta, yolk sac, and embryo proper, the study stated.

Furthermore, they also provide an unlimited cell resource and hold great potential for in vivo disease modeling, in vivo drug discovery, and in vivo tissue generation in the future. Finally, our study opens a path toward capturing stem cells with intra- and/or inter-species bi-potent chimeric competency from a variety of other mammalian species.

Organs for transplant

The creation of chimeric mice is part of Izpisa Bemontes longstanding goal of growing human organs in animals for transplant.

While mice are too small to grow organs for transplant, they serve as a model to understand how cells from a different species, can be grown in a host body. In this new study, the mice served as a model of how well the EPS cells can integrate.

Izpisa Bemonte is now working to translate his research on chimeric mice to pigs, which are large enough to provide human organs. In January, a team he led reported on work with human-pig chimeras, which were not allowed to grow past the embryonic stage. They also created rat-mice chimeras.

The superior chimeric competency of both human and mouse EPS cells is advantageous in applications such as the generation of transgenic animal models and the production of replacement organs, Wu said in a Salk statement. We are now testing to see whether human EPS cells are more efficient in chimeric contribution to pigs, whose organ size and physiology are closer to humans.

We believe that the derivation of a stable stem cell line with totipotent-like features will have a broad and resounding impact on the stem cell field, Izpisua Belmonte said in the statement.

The work was funded by a number of sources. They include: the National Key Research and Development Program of China; the National Natural Science Foundation of China; the Guangdong Innovative and Entrepreneurial Research Team Program; the Science and Technology Planning Project of Guangdong Province, China; the Science and Technology Program of Guangzhou, China; the Ministry of Education of China (111 Project); the BeiHao Stem Cell and Q9 Regenerative Medicine Translational Research Institute; the Joint Institute of Peking University Health Science Center; University of Michigan Health System; Peking-Tsinghua Center for Life Sciences; the National Science and Technology Support Project; the CAS Key Technology Talent Program; the G. Harold and Leila Y. Mathers Charitable Foundation; and The Moxie Foundation.

bradley.fikes@sduniontribune.com

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Stem cell invented that can grow into any tissue in the body - The San Diego Union-Tribune

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'Cradle of life' stem cells taken from skin samples were developed into three-dimensional brain-like organisms capable of exchanging signals between each other in a network.

The petri dish cells behave in a similar way to the brain cells which produce messenger dopamine from neurons - and scientists hope they will be able to use them to come up with a cure for Parkinson's.

Dopamine maintains smooth body movements, but when the neurons die off, tremors, rigid muscles and other Parkinson's disease symptoms begin to take over.

The new developments mean scientists can now use the cells to test what environmental factors like pollutants have on the onset of the disease and potentially find a cure.

Lead author Professor Jens Schwamborn said: "Our cell cultures open new doors to brain research.

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"We can now use them to study the causes of Parkinson's disease and how it could possibly be effectively treated."

Our cell cultures open new doors to brain research

Professor Jens Schwamborn

The stem cells can be transformed into any cell type of the human body but cannot produce a complete organism.

PHD student Anna Monzel developed a procedure to convert the stem cells into brain cells as part of her doctoral thesis.

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Tremor - One of the most noticeable signs of Parkinson's is a tremor that often starts in the hands or fingers when they are relaxed

She said: "I had to develop a special, precisely defined cocktail of growth factors and a certain treatment method for the stem cells, so that they would differentiate in the desired direction."

Prof Schwamborn from the Luxembourg Centre for Systems Biomedicine at Luxembourg University said: "Our subsequent examination of these artificial tissue samples revealed that various cell types characteristic of the midbrain had developed."

"The cells can transmit and process signals.

"We were even able to detect dopaminergic cells - just like in the midbrain."

The scientists say their petri dish study can also reduce the amount of animal testing in brain research.

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Because cell cultures in the petri dishes are of human origin in some aspects they resemble human brains more than the brains of lab animals such as rats or mice.

Professor Schwamborn added: "There are also attractive economic opportunities in our approach.

"The production of tissue cultures is highly elaborate.

"In the scope of our spin-off Braingineering Technologies Sarl, we will be developing technologies by which we can provide the cultures for a fee to other labs or the pharmaceutical industry for their research."

The study was published in the Stem Cell Reports journal.

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Scientists one step closer to turning stem cells into BRAIN | Health ... - Express.co.uk

The most complex organ in humans is the brain. Due to its complexity and, of course, for ethical reasons, it is extremely difficult to do scientific experiments on it -- ones that could help us to understand neurodegenerative diseases like Parkinson's, for example. Scientists at the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg have now succeeded in turning human stem cells derived from skin samples into tiny, three-dimensional, brain-like cultures that behave very similarly to cells in the human midbrain. In the researchers' petri dishes, different cell types develop, connect into a network, exchange signals and produce metabolic products typical of the active brain. "Our cell cultures open new doors to brain research," says Prof. Dr. Jens Schwamborn, in whose LCSB research group Developmental & Cellular Biology the research work was done. "We can now use them to study the causes of Parkinson's disease and how it could possibly be effectively treated." The team publishes its results today in the scientific journal Stem Cell Reports.

The human midbrain is of particular interest to Parkinson's researchers: it is the seat of the tissue structure known medically as the substantia nigra. Here, nerve cells -- specifically dopaminergic neurons -- produce the messenger dopamine. Dopamine is needed to maintain smooth body movements. If the dopaminergic neurons die off, then the person affected develops tremors and muscle rigidity, the distinctive symptoms of Parkinson's disease. For ethical reasons, researchers cannot take cells from the substantia nigra to study them. Research groups around the world are therefore working on cultivating three-dimensional structures of the midbrain in petri dishes. The LCSB team led by stem cell researcher Jens Schwamborn is one such group.

The LCSB scientists worked with so-called induced pluripotent stem cells -- stem cells that cannot produce a complete organism, but which can be transformed into all cell types of the human body. The procedures required for converting the stem cells into brain cells were developed by Anna Monzel as part of her doctoral thesis, which she is doing in Schwamborn's group. "I had to develop a special, precisely defined cocktail of growth factors and a certain treatment method for the stem cells, so that they would differentiate in the desired direction," Monzel describes her approach. To do this, she was able to draw on extensive preparatory work that had been done in Schwamborn's team the years before. The pluripotent stem cells in the petri dishes multiplied and spread out into a three-dimensional supporting structure -- producing tissue-like cell cultures.

"Our subsequent examination of these artificial tissue samples revealed that various cell types characteristic of the midbrain had developed," says Jens Schwamborn. "The cells can transmit and process signals. We were even able to detect dopaminergic cells -- just like in the midbrain." This fact makes the LCSB scientists' results of extraordinary interest to Parkinson's researchers worldwide, as Schwamborn stresses: "On our new cell cultures, we can study the mechanisms that lead to Parkinson's much better than was ever the case before. We can test what effects environmental impacts such as pollutants have on the onset of the disease, whether there are new active agents that could possibly relieve the symptoms of Parkinson's -- or whether the disease could even be cured from its very cause. We will be performing such investigations next."

The development of the brain-like tissue cultures not only opens doors to new research approaches. It can also help to reduce the amount of animal testing in brain research. The cell cultures in the petri dishes are of human origin, and in some aspects resemble human brains more than the brains of lab animals such as rats or mice do. Therefore, the structures of human brains and its modes of function can be modelled in different ways than it is possible in animals. "There are also attractive economic opportunities in our approach," Jens Schwamborn explains: "The production of tissue cultures is highly elaborate. In the scope of our spin-off Braingineering Technologies Sarl, we will be developing technologies by which we can provide the cultures for a fee to other labs or the pharmaceutical industry for their research."

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Materials provided by University of Luxembourg. Note: Content may be edited for style and length.

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Brain tissue from a petri dish: Stem cell research -- ScienceDaily - Science Daily

It will be several weeks before Jonathan Pitre finds out if his second stem-cell transplant was successful. Tina Boileau / -

The perilous wait now begins for Jonathan Pitre.

Pitre, 16, was transfused with blood and marrow drawn from his mothers hip late Thursday afternoon. The stem-cell rich material holds the power to alter the course of Pitres aggressive skin disease, epidermolysis bullosa (EB), and change his life.

So far, so good, saidPitres mother, Tina Boileau.

It will be several weeks before Pitre finds out whether the transplant has worked its magic.

While waiting for that answer, theRussell teenager will have to travel the most difficult part of his medical journey: a time when his immune system is at its lowest ebb, and when he feels the full effects of high-dose chemotherapy and radiation.

His physician, Dr. Jakub Tolar, has warned that the period represents the highest risk for complications, the most common of which are infections and graft-versus-host disease (GVHD). It is a potentially life-threatening situation in which the implanted stem cells produce T-cells that attack normal cells.

In about two weeks time, doctors will start to look for signs that Boileaus stem cells have successfully established themselves in Pitres bone marrow.The presence of white blood cells is one of the earliest signs of stem-cell growth; an improvement in the condition of Pitres skin could also signal that the stem cells have started to work.

Last year, after his first stem-cell transplant, Pitre and his mother were thrilled when doctors discovered new white cells in his bloodstream. But their hopes were crushed when tests showed Pitres own stem cells had recolonized his bone marrow, and were producing the cells.

This time, Boileau said, they will wait to see more lab results before getting their hopes too high.

I think we will have that uncertainly until we know for sure through skin and bone marrow biopsies that the engraftment worked, she said.

Boileau went into surgery early Thursday morning to have blood and bone marrow drawn from her hip. She was at her sons bedside later in the afternoon to watch as the stem cells dripped through an intravenous tube connected to the right atrium of her sons heart.

If the transplant works, Boileaus stem cells will establish themselves in her sons bone marrow, grow, divide and make new blood cells equipped with the power to provide Pitre with the key protein he needs to rebuild his damaged skin.

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His stem-cell transplant complete, the wait begins for Jonathan Pitre - Ottawa Citizen

Over recent years, I have seen a growing interest in stem cells and a particular preparation called Platelet Rich Plasma (PRP). Many famous athletes including Tiger Woods have received PRP for various musculoskeletal problems and some have credited it with their accelerated healing and more rapid return to play.

PRP is plasma, the liquid part of blood, concentrated with many more platelets than typically found there. Platelets are known for their importance in clotting blood, but they also contain hundreds of proteins called growth factors. These are responsible for the cascade of events naturally involved in tissue repair. Your own innate stem cells are attracted to the site of injury and play a critical role in the healing process.

Typically, PRP is isolated from your own blood, drawn in the office while you wait. The highly concentrated growth factors are then delivered back into the body at the site of interest. PRP injections have been used for musculoskeletal problems such as sprained knees, osteoarthritis, and chronic tendon injuries. Previously, these types of conditions were treated with medications, physical therapy, and surgery, but PRP recipients commonly report less pain and stronger, more stable joints. It may even promote new cartilage formation in aging joints enabling you to put off joint replacement surgery.

PRP can also be very effective in treating chronic tendon injuries, especially tennis elbow, a common injury of the tendons on the outside of the elbow. Previously, cortisone injections were commonly used, but we know steroids will ultimately weaken tendons and promote rupture. In contrast, now PRP treatments lead to stronger tendons.

Promoting healing after tendon surgery is another use for PRP. For example, an athlete with a completely torn heel cord may require surgery to repair the tendon. Healing of the torn tendon can potentially be improved by treating the injured area with PRP during surgery. With a shorter recovery time, less chronic pain and stronger tissue, you can see why athletes love PRP!

More recently, PRP is being used extensively in aesthetic medicine to keep us looking younger and to promote hair growth. In the same ways the growth factors in PRP facilitate tissue repair from injury or surgery, they also regenerate aging skin. PRP injected into the facial skin has been called the vampire facial made famous by some Hollywood stars.

Today we use a more advanced technique called micro-needling. The PRP is layered across your face and delivered to the skin using a handheld device called a Micropen. This device has 12 tiny micro-needles that drive the PRP in, calling in the tissue repair team to get to work! The result is accelerated collagen production with new, thicker, stronger collagen. The procedure is well tolerated and done in the office while you are awake. It takes less than a couple of hours to complete and usually two to three treatments are recommended spaced four to six weeks apart. The collagen repair process can take four to six weeks, we expect to see the full results blossom over the course of months and continue to improve over a year.

The best thing about PRP Micropen Facelift is that theres not serious downtime like you get with laser resurfacing or surgery. Plus, unlike dermal fillers, which will fade in months, these results will continue to improve over the year. Most commonly we treat faces, but the procedure is safe to use all over the body including necks, chests, hands, and even eye lids. It is also quite helpful for minimizing and fading stretch marks.

If you have any questions or want to learn more about PRP for musculoskeletal or skin rejuvenation, please plan to attend our free interactive community lecture on this topic at the Coronado Library Winn Room from 6-7PM on Thursday 04/06/2017!

Lauren Mathewson, ND is Board certified in naturopathic medicine and Patrick Yassini, MD is board certified in family medicine, integrative and holistic medicine. They practice at Peak Health Group, 131 Orange Avenue, #100, Coronado, Calif.; the office number is (619) 522-4005.

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Now You Can Harness Your Own Stem Cells - Coronado Eagle ... - Coronado Eagle and Journal

Pennsylvania state trooper Matt Uram was talking with his wife at a July Fourth party in 2009 when a misjudged spray of gasoline burst through a nearby bonfire and set him alight. Flames covered the entire right side of his body, and after he fell to the ground to smother them, his wife beat his head with her bare hands to put out his burning hair. It was only on the way to the ER, as the shock and adrenaline began to wear off, that the pain set in. It was intense, he says. If you can imagine what pins and needles feel like, then replace those needles with matches.

From the hospital, Uram was transferred to the Mercy Burn Center in Pittsburgh, where doctors removed all of the burned skin and dressed his wounds. It was on the border between a second- and third-degree burn, and he was told to prepare for months of pain and permanent disfigurement. Not long after this assessment, however, a doctor asked Uram if he would be willing to take part in an experimental trial of a new device.

The treatment, developed by German researcher Dr. Jrg Gerlach, was the worlds first to use a patients stem cells to directly heal the skin. If successful, the device would mend Urams wounds using his bodys ability to regenerate fully functioning skin. Uram agreed to the procedure without hesitation.

Five days after the accident, surgeons removed a small section of undamaged skin from Urams right thighabout the size of a postage stampand used it to create a liquid suspension of his stem cells that was sprayed in a fine mist onto the damaged skin. Three days later, when it was time to remove the bandages and re-dress the wounds, his doctor was amazed by what he saw. The burns were almost completely healed, and any risk of infection or scarring was gone.

Pennsylvania State Trooper Matt Uram's arm eventually healed without scarring. RenovaCare

A study subsequently published in the scientific journal Burns described how the spray was able to regrow the skin across the burn by spreading thousands of tiny regenerative islands, rather than forcing the wound to heal from its edge to the inside. The technique meant reducing the healing time and minimizing complications, with aesthetically and functionally satisfying outcomes, the paper stated.

Dozens more burn victims in Germany and the U.S. were successfully treated with the spray following Urams procedure, and in 2014 Gerlach sold the technology to RenovaCare. The medical technology startup has now transformed the proof-of-concept device from a complicated prototype into a user-friendly product called a SkinGun, which it hopes clinicians will be able to use outside of an experimental setting. For that to happen, RenovaCare is preparing clinical studies for later this year, with the aim of Food and Drug Administration approval for the SkinGun.

Once these obstacles are overcome, RenovaCare CEO Thomas Bold believes, the SkinGun can compete with, or even replace, todays standard of care.

Current treatment of severe burns involves transplanting healthy skin from one area of the body and stitching it to another in a process called skin grafting or mesh skin grafting. It is a painful procedure that creates an additional wound at the donor site and can cause restricted joint movement because the transplanted skin is unable to grow with the patient. It is able to cover an area only two to three times as large as the harvested patch. The current standard of care is just horrible, says Bold. We are part of regenerative medicineit is the medicine of the future and will be life-changing for patients.

RenovaCare's SkinGun sprays a liquid suspension of a patient's stem cells onto a burn or wound in order to regrow the skin without scars. RenovaCare

Beyond regulatory matters, there are also limitations to the technology that make it unsuitable for competing with treatments of third-degree burns, which involve damage to muscle and other tissue below the skin. Still, stem cell researcher Sarthak Sinha believes that while the SkinGun may not be that advanced yet, it shows the vast potential of this form of regenerative medicine. What I see as the future of burn treatment is not skin repair but rather functional regeneration of skin and its appendagessuch as hair follicles, glands and fat, says Sinha. This could be achieved by engaging deeper layers of skin and its resident stem cells to partake in tissue regeneration.

Research is already underway at RenovaCare to enable treatment of third-degree burns, which Bold describes as definitely within the range of possibility. Bold claims the adaptations to the SkinGun would allow it to treat other damaged organs using a patients stem cells, but for now the company is focusing solely on burns and wounds to skinthe largest organ of the human body.

Urams burns are now completely unnoticeable. There is no scar tissue or even pigment discoloration, and the regenerated skin even tans. If I show someone where I was burnt, I bet $100,000 they couldnt tell, he says. Theres no scars, no residual pain; its like the burn never happened. Its a miracle.

Uram is frustrated that the treatment is not available to other burn victims, particularly children. I want to see the FDA get off their butts and approve this, he says. A grown man like me to be scarred is OK, but think about the kids that have to live the rest of their lives with pain and scarring. Thats not OK.

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Spray-On Skin: 'Miracle' Stem Cell Treatment Heals Burns Without ... - Newsweek

Researchers from the University of Illinois at Chicago have identified a molecular switch that converts skin cells into cells that make up blood vessels, which could ultimately be used to repair damaged vessels in patients with heart disease or to engineer new vasculature in the lab. The technique, which boosts levels of an enzyme that keeps cells young, may also circumvent the usual aging that cells undergo during the culturing process. Their findings are reported in the journal Circulation.

Scientists have many ways to convert one type of cell into another. One technique involves turning a mature cell into a "pluripotent" stem cell -- one that has the ability to become any type of cell -- and then using chemical cocktails to coax it into maturing into the desired cell type. Other methods reprogram a cell so that it directly assumes a new identity, bypassing the stem-cell state.

In the last few years, scientists have begun to explore another method, a middle way, that can turn back the clock on skin cells so that they lose some of their mature cell identity and become more stem-like.

"They don't revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells," says Dr. Jalees Rehman, associate professor of medicine and pharmacology at UIC, who led the team of researchers. Progenitor cells can be grown in large quantities sufficient for regenerative therapies. And unlike pluripotent stem cells, progenitor cells can only differentiate into a few different cell types. Rehman calls this method to produce new cells "partial de-differentiation."

Other groups have used this technique to produce progenitor cells that become blood vessel cells. But until now, researchers had not fully understood how the method worked, Rehman said.

"Without understanding the molecular processes, it is difficult for us to control or enhance the process in order to efficiently build new blood vessels," he said.

His group discovered that the progenitors could be converted into blood vessel cells or into red blood cells, depending on the level of a gene transcription factor called SOX17.

The researchers measured the levels of several genes important for blood vessel formation. They saw that as progenitor cells were differentiating into blood vessel cells, levels of the transcription factor SOX17 became elevated.

When they increased levels of SOX17 even more in the progenitor cells, they saw that differentiation into blood vessel cells was enhanced about five-fold. When they suppressed SOX17, the progenitor cells produced fewer endothelial cells and instead generated red blood cells.

"It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming," Rehman said.

When the researchers embedded the human progenitor cells into a gel and implanted the gels in mice, the cells organized into functional human blood vessels. Skin cells that had not undergone a conversion did not form blood vessels when similarly implanted.

When they implanted the progenitor cells into mice that had sustained heart damage from a heart attack, the implanted cells formed functional human blood vessels in the mouse hearts -- and even connected with existing mouse blood vessels to significantly improve heart function.

The human adult skin cells used by Rehman's team can easily be obtained by a simple skin biopsy.

"This means that one could generate patient-specific blood vessels or red blood cells for any individual person," Rehman said. Using such personalized cells reduces the risk of rejection, he said, because the implanted blood vessels would have the same genetic makeup as the recipient.

Rehman and his colleagues noticed something else about the progenitor cells -- they had elevated levels of telomerase -- the "anti-aging" enzyme that adds a cap, or telomere, to the ends of chromosomes. As the caps wear away a little bit each time a cell divides, they are believed to contribute to aging in cells, whether in the body or growing in culture in the laboratory.

"The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients," Rehman said. "Their cells may already have shortened telomeres due to their advanced age. The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature aging."

While telomerase has benefits, the enzyme is also found in extremely high levels in cancer cells, where it keeps cell division in overdrive.

"We were concerned about the risk of tumor formation," Rehman said, but the researchers didn't observe any in these experiments. "But to truly determine the efficacy and safety of these cells for humans, one needs to study them over even longer time periods in larger animals."

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Turning skin cells into blood vessel cells while keeping them young - Science Daily

Mouse heart section showing human progenitor cells that formed functional human blood vessels. Purple color signifies human blood vessels, red staining signifies the blood vessels of the mouse that received the human cell implants. Credit: UIC

Researchers from the University of Illinois at Chicago have identified a molecular switch that converts skin cells into cells that make up blood vessels, which could ultimately be used to repair damaged vessels in patients with heart disease or to engineer new vasculature in the lab. The technique, which boosts levels of an enzyme that keeps cells young, may also circumvent the usual aging that cells undergo during the culturing process. Their findings are reported in the journal Circulation.

Scientists have many ways to convert one type of cell into another. One technique involves turning a mature cell into a pluripotent stem cell one that has the ability to become any type of cell and then using chemical cocktails to coax it into maturing into the desired cell type. Other methods reprogram a cell so that it directly assumes a new identity, bypassing the stem-cell state.

In the last few years, scientists have begun to explore another method, a middle way, that can turn back the clock on skin cells so that they lose some of their mature cell identity and become more stem-like.

They dont revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells, says Dr. Jalees Rehman, associate professor of medicine and pharmacology at UIC, who led the team of researchers. Progenitor cells can be grown in large quantities sufficient for regenerative therapies. And unlike pluripotent stem cells, progenitor cells can only differentiate into a few different cell types. Rehman calls this method to produce new cells partial de-differentiation.

Other groups have used this technique to produce progenitor cells that become blood vessel cells. But until now, researchers had not fully understood how the method worked, Rehman said.

Without understanding the molecular processes, it is difficult for us to control or enhance the process in order to efficiently build new blood vessels, he said.

His group discovered that the progenitors could be converted into blood vessel cells or into red blood cells, depending on the level of a gene transcription factor called SOX17.

The researchers measured the levels of several genes important for blood vessel formation. They saw that as progenitor cells were differentiating into blood vessel cells, levels of the transcription factor SOX17 became elevated.

When they increased levels of SOX17 even more in the progenitor cells, they saw that differentiation into blood vessel cells was enhanced about five-fold. When they suppressed SOX17, the progenitor cells produced fewer endothelial cells and instead generated red blood cells.

It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming, Rehman said.

When the researchers embedded the human progenitor cells into a gel and implanted the gels in mice, the cells organized into functional human blood vessels. Skin cells that had not undergone a conversion did not form blood vessels when similarly implanted.

When they implanted the progenitor cells into mice that had sustained heart damage from a heart attack, the implanted cells formed functional human blood vessels in the mouse hearts and even connected with existing mouse blood vessels to significantly improve heart function.

The human adult skin cells used by Rehmans team can easily be obtained by a simple skin biopsy.

This means that one could generate patient-specific blood vessels or red blood cells for any individual person, Rehman said. Using such personalized cells reduces the risk of rejection, he said, because the implanted blood vessels would have the same genetic makeup as the recipient.

Rehman and his colleagues noticed something else about the progenitor cells they had elevated levels of telomerase the anti-aging enzyme that adds a cap, or telomere, to the ends of chromosomes. As the caps wear away a little bit each time a cell divides, they are believed to contribute to aging in cells, whether in the body or growing in culture in the laboratory.

The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients, Rehman said. Their cells may already have shortened telomeres due to their advanced age. The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature aging.

While telomerase has benefits, the enzyme is also found in extremely high levels in cancer cells, where it keeps cell division in overdrive.

We were concerned about the risk of tumor formation, Rehman said, but the researchers didnt observe any in these experiments. But to truly determine the efficacy and safety of these cells for humans, one needs to study them over even longer time periods in larger animals.

Reference:

Zhang, L., Jambusaria, A., Hong, Z., Marsboom, G., Toth, P. T., Herbert, B., . . . Rehman, J. (2017). SOX17 Regulates Conversion of Human Fibroblasts into Endothelial Cells and Erythroblasts via De-Differentiation into CD34 Progenitor Cells. Circulation. doi:10.1161/circulationaha.116.025722

This article has been republished frommaterialsprovided by the University of Illinois at Chicago. Note: material may have been edited for length and content. For further information, please contact the cited source.

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Partial De-differentiation Converts Skin Cells into Blood Vessel Cells - Technology Networks

As a kid, I was always intrigued with potions and products. My father worked as a scientist, whose specialty was chemistry as well as business. For many years he worked as the Director of Research and Development for the Mennen Company. Perhaps this is where my love of products and researching products began.

Like many women, my skin can be difficult at times. I have eczema which makes it intermittently sensitive, so I have to be careful of the products I use. While researching these products, I also looked into the science supporting them.

As fate would have it while exploring some interesting articles on my Twitter feed recently, I came across an intriguing tweet I just couldnt ignore. It was a tweet by a glamorous NYC dermatologist who was talking about how excited she was to receive her Lifeline Skin Care products in the mail. Her excitement was so infectious; I decided to look into these products for myself; and looking into them, ultimately led to me buy them.

While researching Lifeline Skin Cares products, I also looked into the science supporting them. Lifeline Skin Care products use something I had never heard of before; they use human, non-embryonic stem cells as one of the main ingredients to help tone and reduce the signs of aging.

Science

As a therapist, I not only look for products that work well and that I believe in, but also look at the philosophy of the company. Lifeline Skin Care was a socially conscious company and fit that standard.

Clinical Trials

The original goal for these researchers was to find a cure for diabetes and Parkinsons disease. These scientists created the first non-embryonic human stem cells. This discovery made finding cures for Parkinsons disease and corneal disease more promising. Currently, some of ISCOs most promising research is in the field of Parkinsons disease.

Parkinsons disease (PD) is a long-term degenerative disease of the central nervous system. It mainly affects the motor system and its symptoms usually have a slow-onset. In early stages, the disease is characterized by shaking, slow movement, difficulty in walking, and rigidity. In time, thinking and behavioral problems may occur. Advanced stages of the disease bring dementia.

istock jm1366

International Stem Cell Corporation (ISCO), is the parent company of Lifeline Skin Care and has devoted many years of research to improve this terrible disease. The company has developed a unique method of creating human neural stem cells which when introduced into the brain, promote the recovery of dopaminergic neurons, the brain cells that are originally affected and cause the disease symptoms. ISCOs preclinical studies showed that the administration of these neural stem cells were safe and improved motor symptoms. To date, 3 of the planned total of 12 patients, have entered the clinical trial and have received neural stem cells. At this point in time, all patients have been discharged from their hospital settings and are observed to be meeting clinical expectations.

Lifeline Skin care (LSC) - a subsidiary of ISCO - uses the extracts from human stem cells, (produced by ISCO), and developed for the skin in order to improve the signs of ageing. The latest technology being used to advance a cure for PD is now available for the skin in a line of products produced by LSC. The profits from the sale of these skin care products go directly to ISCO in order to fund the development of a therapy for PD.

From a skincare perspective, not only did Lifeline Skin Cares products feel good on my face, but I started to notice that my skin appeared brighter and less wrinkles, especially around my eyes (love that!).

From a psychological perspective, the younger we look and feel, the more optimistic and hopeful we tend to be about life and future options. I like the idea of feeling young, looking forever fabulous and most of all, being healthy.

Fortunately, Lifeline Skin Care found a way to help women and men look and feel their very best while scientists from their parent company work toward eradicating illness by using their special non-embryonic stem cell technology. Beauty is more than skin-deep; beauty can be on a mission, too.

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The International Stem Cell Corporation, a Company Dedicated to Curing Parkinson's Disease - Huffington Post

M

ice that walk straight and fluidly dont usually make scientists exult, but these did: The lab rodents all had a mouse version of Parkinsons disease and only weeks before had barely been able to lurch and shuffle around their cages.

Using a trick from stem-cell science, researchers managed to restore the kind of brain cells whose death causes Parkinsons. And the mice walked almost normally.The same technique turned human brain cells, growing in a lab dish, into the dopamine-producing neurons that are AWOL in Parkinsons, scientists at Swedens Karolinska Institute reportedon Monday in Nature Biotechnology.

Success in lab mice and human cells is many difficult steps away from success in patients. The study nevertheless injected new life into a promising approach to Parkinsons that has suffered setback after setback replacing the dopamine neurons that are lost in the disease, crippling movement and eventually impairing mental function.

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This is not going to happen in five years or possibly even 10, but Im excited about the potential of this kind of cell replacement therapy, said James Beck, chief scientific officer of the Parkinsons Foundation, which was not involved in the study. It could really give life back to someone with Parkinsons disease.

There is no cure for Parkinsons, a neurodegenerative disease that affects an estimated 10 million people worldwide, most prominently actor Michael J. Fox. Drugs that enable the brain to make dopamine help only somewhat, often causing movement abnormalities called dyskinesia as well as bizarre side effects such as a compulsion to gamble; they do nothing to stop the neurodegeneration.

As Parkinsons patients wait, Fox Foundation and scientist feud over drug trial

Rather than replacing the missing dopamine, scientists led by Karolinskas Ernest Arenas tried to replace dopamine neurons but not in the way that researchers have been trying since the late 1980s. In that approach, scientists obtained tissue containing dopamine neurons from first-trimester aborted fetuses and implanted it intopatients brains.Although a 2001clinical trialfound that the transplants partly alleviated the rigidity and tremors of Parkinsons, the procedure caused serious dyskinesia in about 20 percent of patients, Beck said. More problematic is that fetal issue raises ethical concerns and is in short supply.

It was clear that usable fragments of brain tissue were extremely difficult to recover, said Dr. Curt Freed, of the University of Colorado, who pioneered that work.

Instead, several labs have therefore used stem cells to produce dopamine neurons in dishes. Transplanted into the brains of lab rats with Parkinsons, the neurons reduced rigidity, tremor, and other symptoms. Human studies are expected to begin in the US and Japan this year or next, Beck said.

In the Karolinska approach, there is no need to search for donor cells and no cell transplantation or [need for] immunosuppression to prevent rejection, Arenas told STAT. Instead, he and his team exploited one of the most startling recent discoveries in cell biology: that certain molecules can cause one kind of specialized cell, such as a skin cell, to pull a Benjamin Button, aging in reverse until they become like the embryonic cells called stem cells. Those can be induced to morph into any kind of cell heart, skin, muscle, and more in the body.

Muhammad Ali and Parkinsons disease: Was boxing to blame?

Arenas and his team filled harmless lentiviruses with a cocktail of four such molecules. Injected into the brains of mice with Parkinsons-like damage, the viruses infected plentifulbrain cells called astrocytes. (The brains support cells, astrocytes perform jobs like controlling blood flow.)The viruses also infected other kinds of cells, but their payload was designed to work only in astrocytes, and apparently caused no harm to the other cells.

The molecules, called transcription factors, reprogrammed some of the astrocytes to become dopamine neurons, which were first detected three weeks later in the mouse brains. The dopamine neurons were abundant 15 weeks later, an indication that after changing into dopamine neurons the astrocytes stayed changed.

Five weeks after receiving the injections, the mice, which used to have Parkinsons-like gait abnormalities, walked as well as healthy mice. That suggests that direct reprogramming [of brain cells] has the potential to become a novel therapeutic approach for Parkinsons, Arenas told STAT.

That could have value for preserving the brain circuitry destroyed by Parkinsons, said Colorados Freed.

A lot of hurdles need to be overcome before this becomes a Parkinsons treatment. The Trojan horse system for delivering the reprogramming molecules inside viruseswould need to turn more astrocytes into dopamine neurons and leave other kinds of cells alone: Although viruses getting into mouse brain cells apparently caused no harm, that might not be so in people. We will need to use virus with selective [attraction] for astrocytes, Arenas said.

The morphed cells would presumably be ravaged by whatever produced Parkinsons in the first place. But in other cell transplants, Arenas said, the disease catches up with transplanted cells in 15 to 20 years, buying patients a good period of time. He thinks it might be possible to give patients a single injection but hold off some of the reprogramming with a drug, turning it on when the brain again runs short of dopamine neurons.

The basic technology to develop such strategies currently exists, he said.

The Karolinska lab is working to make the techniquesafer and more effective, including by using viruses that would deliver reprogramming molecules only to astrocytes. We are open to collaborations aimed at human studies, Arenas said.

Would patients be willing to undergo brain injections? People with Parkinsons disease, Beck said, are willing to go through a lot for any hope of improvement.

Sharon Begley can be reached at sharon.begley@statnews.com Follow Sharon on Twitter @sxbegle

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Mighty morphed brain cells cure Parkinson's in mice, but human trials still far off - STAT

Science Daily

Stem cell drug screen yields potential alternative to statins Science Daily Next, they generated induced pluripotent stem cells from these skin cells. Stem cells continually double their numbers while in culture. This meant that a sample of converted skin cells from a single patient with FH provided a renewable source of liver ...

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Stem cell drug screen yields potential alternative to statins - Science Daily

April 6, 2017 A mouse heart section showing human progenitor cells that formed functional human blood vessels. Purple color signifies human blood vessels, red staining signifies the blood vessels of the mouse that received the human cell implants. Credit: Jalees Rehman.

Researchers from the University of Illinois at Chicago have identified a molecular switch that converts skin cells into cells that make up blood vessels, which could ultimately be used to repair damaged vessels in patients with heart disease or to engineer new vasculature in the lab. The technique, which boosts levels of an enzyme that keeps cells young, may also circumvent the usual aging that cells undergo during the culturing process. Their findings are reported in the journal Circulation.

Scientists have many ways to convert one type of cell into another. One technique involves turning a mature cell into a "pluripotent" stem cellone that has the ability to become any type of celland then using chemical cocktails to coax it into maturing into the desired cell type. Other methods reprogram a cell so that it directly assumes a new identity, bypassing the stem-cell state.

In the last few years, scientists have begun to explore another method, a middle way, that can turn back the clock on skin cells so that they lose some of their mature cell identity and become more stem-like.

"They don't revert all the way back to a pluripotent stem cell, but instead turn into intermediate progenitor cells," says Dr. Jalees Rehman, associate professor of medicine and pharmacology at UIC, who led the team of researchers. Progenitor cells can be grown in large quantities sufficient for regenerative therapies. And unlike pluripotent stem cells, progenitor cells can only differentiate into a few different cell types. Rehman calls this method to produce new cells "partial de-differentiation."

Other groups have used this technique to produce progenitor cells that become blood vessel cells. But until now, researchers had not fully understood how the method worked, Rehman said.

"Without understanding the molecular processes, it is difficult for us to control or enhance the process in order to efficiently build new blood vessels," he said.

His group discovered that the progenitors could be converted into blood vessel cells or into red blood cells, depending on the level of a gene transcription factor called SOX17.

The researchers measured the levels of several genes important for blood vessel formation. They saw that as progenitor cells were differentiating into blood vessel cells, levels of the transcription factor SOX17 became elevated.

When they increased levels of SOX17 even more in the progenitor cells, they saw that differentiation into blood vessel cells was enhanced about five-fold. When they suppressed SOX17, the progenitor cells produced fewer endothelial cells and instead generated red blood cells.

"It makes a lot of sense that SOX17 is involved because it is abundant in developing embryos when blood vessels are forming," Rehman said.

When the researchers embedded the human progenitor cells into a gel and implanted the gels in mice, the cells organized into functional human blood vessels. Skin cells that had not undergone a conversion did not form blood vessels when similarly implanted.

When they implanted the progenitor cells into mice that had sustained heart damage from a heart attack, the implanted cells formed functional human blood vessels in the mouse heartsand even connected with existing mouse blood vessels to significantly improve heart function.

The human adult skin cells used by Rehman's team can easily be obtained by a simple skin biopsy.

"This means that one could generate patient-specific blood vessels or red blood cells for any individual person," Rehman said. Using such personalized cells reduces the risk of rejection, he said, because the implanted blood vessels would have the same genetic makeup as the recipient.

Rehman and his colleagues noticed something else about the progenitor cells - they had elevated levels of telomerase - the "anti-aging" enzyme that adds a cap, or telomere, to the ends of chromosomes. As the caps wear away a little bit each time a cell divides, they are believed to contribute to aging in cells, whether in the body or growing in culture in the laboratory.

"The increase in telomerase we see in the progenitor cells could be an added benefit of using this partial de-differentiation technique for the production of new blood vessels for patients with cardiac disease, especially for older patients," Rehman said. "Their cells may already have shortened telomeres due to their advanced age. The process of converting and expanding these cells in the lab could make them age even further and impair their long-term function. But if the cells have elevated levels of telomerase, the cells are at lower risk of premature aging."

While telomerase has benefits, the enzyme is also found in extremely high levels in cancer cells, where it keeps cell division in overdrive.

"We were concerned about the risk of tumor formation," Rehman said, but the researchers didn't observe any in these experiments. "But to truly determine the efficacy and safety of these cells for humans, one needs to study them over even longer time periods in larger animals."

Explore further: Adult stem cells help build human blood vessels in engineered tissues

More information: Lianghui Zhang et al, SOX17 Regulates Conversion of Human Fibroblasts into Endothelial Cells and Erythroblasts via De-Differentiation into CD34Progenitor Cells, Circulation (2017). DOI: 10.1161/CIRCULATIONAHA.116.025722

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Turning skin cells into blood vessel cells while keeping them young - Medical Xpress

Scientists at the Medical University of South Carolina (MUSC) have found that a class of heart failure drugs might decrease low-density lipoprotein (LDL) cholesterol levels in patients who do not respond to statins. In a study appearing in the April 6, 2017 issue ofCell Stem Cell, cardiac glycosides reduced levels of a precursor of LDL in liver-like cells, and patients taking cardiac glycosides for heart failure had low LDL.

Not everyone with high LDL cholesterol responds to statins. Statins increase levels of a cell surface receptor that removes LDL cholesterol from the bloodstream. However, statins do not work in patients with familial hypercholesterolemia (FH), who have a rare mutation in that receptor. FH patients have very high cholesterol and die of cardiovascular disease by their forties. The existing drugs for FH can cause fatty liver disease, and the best treatment is a liver transplant.

Stephen A. Duncan, D. Phil., SmartStateTMChair of Regenerative Medicine at MUSC, and his colleagues, including Max A. Cayo, Ph.D., an MSTP student at the Medical College of Wisconsin, developed a drug screen to identify an alternative to statins. They focused on apolipoprotein B (ApoB), a molecule that liver cells use to make LDL and which is normal in patients with FH. Drugs that decrease ApoB could potentially lower cholesterol independently of the LDL receptor in FH patients and also in patients with other forms of high cholesterol.

FH was a perfect model for testing alternatives to statins. Yet the rarity of FH meant these liver cells were scarce. Duncan's group obtained skin cells from a patient with the rare disorder from the Next Generation Genetic Association Studies consortium of the National Heart, Lung, and Blood Institute, which studies genetic mutations linked to cardiovascular diseases. Next, they generated induced pluripotent stem cells from these skin cells. Stem cells continually double their numbers while in culture. This meant that a sample of converted skin cells from a single patient with FH provided a renewable source of liver-like cells that retained the mutation.

The team treated their liver-like cells with the SPECTRUM drug library, a collection of 2300 pharmaceuticals, many of which have reached clinical trials. In a surprising finding, all nine cardiac glycosides in the library, some once widely prescribed for heart failure, reduced ApoB levels in liver-like cells from the patient with FH, ranging from 29 percent (ouabain) to 38 percent (digoxin) to 73 percent (gitoxin). In further tests, they also lowered ApoB levels in human hepatocytes and reduced them by 30 percent in mice engineered to grow normal human livers without the FH mutation at doses eight times below their toxicity thresholds. Molecular tests revealed that glycosides shorten the lifetime of the ApoB molecule, in part by increasing how quickly it is degraded.

As everyone needs ApoB to make LDL cholesterol, this was proof that cardiac glycosides could potentially also work in patients with other forms of high cholesterol. To find out, the team combed through more than five thousand records of patients prescribed cardiac glycosides for heart failure who also had LDL cholesterol records. On average, LDL cholesterol levels were lower in those taking a cardiac glycoside (reduction of 9 mg/dL) or a statin (reduction of 14 mg/dL) than in those not taking any drug. No difference in LDL cholesterol levels was noted between those taking an angiotensin-converting enzyme inhibitor, another heart failure drug with no known role in cholesterol production, and those not taking any drug. Duncan's team also found patients who had LDL measurements recorded both before and after being prescribed a cardiac glycoside. LDL cholesterol dropped in 16 out of 21 patients and by an average of nearly 26 points, which was similar to the 32-point drop seen in a matching group of patients prescribed statins.

This study contains the first evidence to date that cardiac glycosides could potentially reduce LDL cholesterol independently of the LDL receptor, where statins act, by promoting ApoB degradation.

It is not clear from this study whether cardiac glycosides decrease LDL cholesterol in patients who do not have heart failure or at what dose they should be used. The cardiac glycosides have narrow ranges of efficacy for the treatment of heart failure, above which they can be toxic. However, they could offer inexpensive, life-saving options for patients with FH. Digoxin, the cardiac glycoside most commonly prescribed for heart failure, costs less than one dollar per day. Additionally, a cardiac glycoside in a low dose could conceivably provide an added benefit to patients already taking a statin. Finally, using stem cell-based screens of drugs that are already on the market is an innovative way to investigate treatments for rare liver diseases.

"There are so few livers available for transplant," says Duncan. "Having the stem cell model where we make liver cells in the culture dish opens up a possibility of using this not only to investigate a disease, but also as a way to discover drugs that could fix a disease."

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Stem Cell Drug Screen Yields Potential Alternative to Statins - R & D Magazine

Using 3D tissues generated from stem cells, scientists in Germany were able to gain insights into a hereditary disorder which affects parts of brain.

Scientists have grown 3D mini-brains from stem cells and used them to better understand how a rare congenital brain defect develops.

A new method could push research into developmental brain disorders an important step forward, researchers said. Scientists at the University of Bonn in Germany converted skin cells from patients into induced pluripotent stem cells.

From these jack-of-all-trades cells, they generated brain organoids small 3D tissues which resemble the structure and organisation of the developing human brain.

Investigations into human brain development using human cells in the culture dish have so far been very limited: the cells in the dish grow flat, so they do not display any three-dimensional structure.

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Model organisms are available as an alternative, such as mice. The human brain has, however, a much more complex structure. Developmental disorders of the human brain can thus only be resembled to a limited degree in the animal model.

Scientists at the University of Bonn applied a recent development in stem cell research to tackle this limitation: they grew 3D organoids in the cell culture dish, the structure of which is incredibly similar to that of the human brain.

These mini brains offer insight into the processes with which individual nerve cells organise themselves into our highly complex tissues. In their work, the scientists investigated the Miller-Dieker syndrome a hereditary disorder is attributed to a chromosome defect. As a consequence, patients present malformations of important parts of their brain.

In patients, the surface of the brain is hardly grooved but instead more or less smooth, said Vira Iefremova, from University of Bonn. The researchers produced induced pluripotent stem cells from skin cells of Miller-Dieker patients, from which they then grew brain organoids.

In organoids, the brain cells organise themselves very similar to the process in the brain of an embryo: the stem cells divide; a proportion of the daughter cells develops into nerve cells; these move to wherever they are needed.

In organoids, the brain cells organise themselves very similar to the process in the brain of an embryo. (Shutterstock)

These processes resemble a complicated orchestral piece in which the genetic material waves the baton. In Miller-Dieker patients, this process is fundamentally disrupted.

We were able to show that the stem cells divide differently in these patients, said Philipp Koch, associate professor from the University of Bonn. In healthy people, the stem cells initially extensively multiply and form organised, densely packed layers. Only a small proportion of them becomes differentiated and develops into nerve cells, said Koch, who led the study.

Certain proteins are responsible for the dense and even packing of the stem cells. The formation of these molecules is disrupted in Miller-Dieker patients.

The stem cells are thus not so tightly packed and, at the same time, do not have such a regular arrangement. This poor organisation leads, among other things, to the stem cells becoming differentiated at an earlier stage.

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3D 'mini-brains' help understand rare developmental disorders - Hindustan Times

Its tough being a kid, when No seems to be the primary component in an adults vocabulary. Dont jump on the bed, Dont touch the hot pan, and, my personal favorite as a parent, No, you may not color your sister with permanent markers.

Being a young, developmentally impressionable cell is also no picnic. How to choose what developmental path to follow? Should it become a nerve cell, a skin cell, a muscle cell? Now stem cell researcher Marius Wernig, MD, along with postdoctoral scholarMoritz Mall, PhD, and former postdoctoral scholar Michael Kareta, PhD,have shown that young would-be neural cells also live in a culture of no in the form of a powerful repressor protein called Myt1l that actively blocks all other cell fates including skin, heart, lung and liver.

They published their results yesterday in Nature.

As I explained in our release:

The study marks the first identification of a near-global repressor that works to block many cell fates but one. It also suggests the possibility of a network of as-yet-unidentified master regulators specific to each cell type in the body.

Myt1l works in conjunction with another protein that channels the developing cell into the neural cell fate by encouraging the expression of nerve-specific genes. Wernig explained:

Together, these proteins work as a perfect team to funnel a developing cell, or a cell that is being reprogrammed, into the desired cell fate Its a beautiful scenario that both blocks the fibroblast program and promotes the neuronal program. My gut feeling would be that there are many more master repressors like Myt1l to be found for specific cell types, each of which would block all but one cell fate.

Blocking Myt1l expression even in adult neural cells can cause them to lose their way, the researchers found. They begin to express non-neuronal genes and become less efficient at transmitting nerve signals.Because Myt1l has been found to be mutated in some cases of autism, schizophrenia and major depression, theresearch may one day offer new therapeutic avenues for affected people.

Wernig is a member of StanfordsInstitute for Stem Cell Biology and Regenerative Medicine.

Previously: Bridging the stem-cell gap: Stanford researchers identify unique transition state,Its not just science fiction anymore: Childx speakers talk stem cell and gene therapyandCongratulations to Marius Wernig, named Outstanding Young Investigator by stem cell society Image by Gemma Evans

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No means no in stem cell fates, say Stanford researchers - Scope (blog)

Associate professor Dr. Philipp Koch, Dr. Julia Ladewig and Vira Iefremova. Credit: Barbara Frommann/Uni Bonn

A new method could push research into developmental brain disorders an important step forward. This is shown by a recent study at the University of Bonn in which the researchers investigated the development of a rare congenital brain defect. To do so, they converted skin cells from patients into so called induced pluripotent stem cells. From these jack-of-all-trades cells, they generated brain organoids small three-dimensional tissues which resemble the structure and organization of the developing human brain.

Investigations into human brain development using human cells in the culture dish have so far been very limited: the cells in the dish grow flat, so they do not display any three-dimensional structure. Model organisms are available as an alternative, such as mice. The human brain has, however, a much more complex structure. Developmental disorders of the human brain can thus only be resembled to a limited degree in the animal model.

Scientists at the Institute of Reconstructive Neurobiology at the University of Bonn applied a recent development in stem cell research to tackle this limitation: they grew three-dimensional organoids in the cell culture dish, the structure of which is incredibly similar to that of the human brain. These mini brains offer insight into the processes with which individual nerve cells organize themselves into our highly complex tissues. The method thus opens up completely new opportunities for investigating disorders in the architecture of the developing human brain, explains Dr. Julia Ladewig, who leads a working group on brain development.

Rare brain deformity investigated

In their work, the scientists investigated the Miller-Dieker syndrome. This hereditary disorder is attributed to a chromosome defect. As a consequence, patients present malformations of important parts of their brain. In patients, the surface of the brain is hardly grooved but instead more or less smooth, explains Vira Iefremova, PhD student and lead author of the study. What causes these changes has so far only been known in part.

The researchers produced induced pluripotent stem cells from skin cells from Miller-Dieker patients, from which they then grew brain organoids. In organoids, the brain cells organize themselves very similar to the process in the brain of an embryo: the stem cells divide; a proportion of the daughter cells develops into nerve cells; these move to wherever they are needed. These processes resemble a complicated orchestral piece in which the genetic material waves the baton.

In Miller-Dieker patients, this process is fundamentally disrupted. We were able to show that the stem cells divide differently in these patients, explains associate professor Dr. Philipp Koch, who led the study together with Dr. Julia Ladewig. In healthy people, the stem cells initially extensively multiply and form organized, densely packed layers. Only a small proportion of them becomes differentiated and develops into nerve cells.

Certain proteins are responsible for the dense and even packing of the stem cells. The formation of these molecules is disrupted in Miller-Dieker patients. The stem cells are thus not so tightly packed and, at the same time, do not have such a regular arrangement. This poor organization leads, among other things, to the stem cells becoming differentiated at an earlier stage. The change in the three-dimensional tissue structure thus causes altered division behavior, says Ladewig. This connection cannot be identified in animals or in two-dimensional cell culture models.

The scientist emphasizes that no new treatment options are in sight as a result of this. We are undertaking fundamental research here. Nevertheless, our results show that organoids have what it takes to herald a new era in brain research. And if we better understand the development of our brain, new treatment options for disorders of the brain can presumably arise from this over the long term.

Reference:

Iefremova, V., Manikakis, G., Krefft, O., Jabali, A., Weynans, K., Wilkens, R., . . . Ladewig, J. (2017). An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome. Cell Reports, 19(1), 50-59. doi:10.1016/j.celrep.2017.03.047

This article has been republished frommaterialsprovided by the University of Bonn. Note: material may have been edited for length and content. For further information, please contact the cited source.

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'Mini Brains' Developed to Study Miller-Dieker Syndrome ... - Technology Networks