Luxembourg (Scicasts) Stem cells are unspecialized cells that can develop into any type of cell in the human body. So far, however, scientists only partially understand how the body controls the fate of these all-rounders, and what factors decide whether a stem cell will differentiate, for example, into a blood, liver or nerve cell. Researchers from the Luxembourg Centre for Systems Biomedicine (LCSB) of the University of Luxembourg and an international team have now identified an ingenious mechanism by which the body orchestrates the regeneration of red and white blood cells from progenitor cells. "This finding can help us to improve stem cell therapy in future," says Dr. Alexander Skupin, head of the "Integrative Cell Signalling" group of LCSB. The LCSB team has published its results in the scientific journal PLOS Biology.

Although all cells in an organism carry the same genetic blueprints -- the same DNA -- some of them act as blood or bone cells, for example, while others function as nerve or skin cells. Researchers already understand quite well how individual cells work. But how an organism is able to create such a diversity of cells from the same genetic template and how it manages to relocate them to wherever they are needed in the body is still largely unknown.

In order to learn more about this process, Alexander Skupin and his team treated blood stem cells from mice with growth hormones and then watched closely how these progenitor cells behaved during their differentiation into white or red blood cells. The researchers observed that the cells' transformation does not occur in linear, targeted fashion, but rather more opportunistically. Each progenitor cell adapts to the needs of its environment and integrates itself into the body where new cells are needed. "So, it is not as though the cell takes a ticket at the beginning of its differentiation and then travels straight to its destination. Rather, it gets off frequently to look around and see which line is best to take," Alexander Skupin explains. By this clever mechanism, a multicellular organism can adapt the regrowth of new cells to its current needs. "Before progenitor cells differentiate once and for all, they first lose their stem cell character and then check, as it were, which cell line is currently in demand. Only then do they develop into the cell type that best suits their characteristics and which prevails in their environment," Alexander Skupin says.

The researcher likens this step to a game of roulette, where the different types of cells can be thought of as the differently numbered slots in the roulette wheel that catch the ball. "When the cells lose their stem cell character, they are quasi thrown into the roulette wheel, where they first bounce around aimlessly. Only when they have found the right environment do the cells then drop into that niche - like the roulette ball falling into a numbered slot - and differentiate definitively." This way, the body can orchestrate its cell regeneration and at the same time prevent stem cells from being misdirected too early. "Even if a cell takes a wrong turn, it is ultimately sorted out again if its characteristics are unsuitable for the niche, or slot, it has landed in," says Skupin.

With their study, Alexander Skupin and his team have shown for the first time that a progenitor cell's fate is not clearly predetermined and does not follow a straight line. "This observation contradicts the current doctrine that stem cells are programmed to follow a certain lineage from the beginning," Alexander Skupin says. The researcher is furthermore convinced that the processes are similar for other progenitor cells. "In the lab, we have observed the same differentiation pattern in so-called iPS cells, or induced pluripotent stem cells, which can transform into many different types of cells."

This knowledge can help the researchers to improve the effectiveness of therapies in future. Stem cell therapy involves administering a patient his or her own body's stem cells in order to replace other cells that have died as a result of an affliction such as Parkinson's disease. While this promising treatment method has been intensively researched over many years, there has so far been only limited practical success in endogenous stem cell therapy. It is also highly controversial, since it is frequently accompanied by severe side effects and it cannot be ruled out that some cells might degenerate and lead to cancer. "Because we now have a better understanding of how the body influences the direction in which stem cells differentiate, we can hopefully control this process better in future," Alexander Skupin concludes.

Article adapted from a University of Luxembourg news release.

Publication: Cell Fate Decision as High-Dimensional Critical State Transition. Mitra Mojtahedi et al. PLoS Biol. (2016): Click here to view.

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Team Deciphers How the Body Controls Stem Cells - Scicasts (press release) (blog)

March 17, 2017 Left: Cross-sectional view of the cerebrum in normal ferret. Neurons are localized in the cerebral cortex, the surface layer of the cerebrum. Since the surface of the cerebrum has folds (gyri), the layer containing neurons winds on its way. Right: Cross-sectional view of the cerebrum in TD ferret. Clusters of neurons (indicated by arrows) are found deep in the cerebrum, which are not detected in the cerebrum of normal ferret. They are called 'periventricular nodular heterotopia,' PNH. In addition, in the surface layer, a larger number of smaller folds (gyri) are seen than normal (indicated by asterisks). They are called polymicrogryri. Credit: Kanazawa University

Thanatophoric dysplasia (TD) is an intractable disease causing abnormalities of bones and the brain. In a recent study of ferrets, which have brains similar to those of humans, researchers using a newly developed technique discovered that neuronal translocation along radial glial fibers to the cerebral cortex during fetal brain development is aberrant, suggesting the cause underlying TD.

In TD cases, the limb and rib bones are shorter than normal, and brain abnormalities manifest, including polymicrogyria and periventricular nodular heterotopia. Previous research has determined that a gene, fibroblast growth factor receptor 3 (FGFR3), is responsible. However, as a result of TD rarity and the difficulty of obtaining brain samples from human patients, the pathophysiology of TD is largely unknown, and effective therapy has not been established.

The present research team of Kanazawa University generated an animal model of TD using ferrets that reproduces the brain abnormalities found in human TD patients. By using this animal model, the team elucidated the formation process of polymicrogyria, one of the abnormalities found in the TD brain. The team has also investigated the formation process of PNH, the other brain abnormality found in human TD patients.

First, PNH was analyzed in terms of composing cell types to reveal that a large number of neurons but few glial cell exist in PNH. In a healthy brain, neurons are found in the cerebral cortex near the brain surface. The researchers believe that during fetal brain development, PNH formation might be induced by the inability of neurons to translocate themselves to the cerebral cortex. The researchers found that the spatial arrangement of radial glial cells was distorted; radial glial fibers are believed to serve as the "track" for neurons to translocate themselves. Thus, the distortion of radial glial fibers seems to be a reason for aberrant localization of neurons.

Research on abnormalities of bones in TD is progressing with iPS cells at Kyoto University, and it is expected that the whole aspect of TD with brain and bone abnormalities would be elucidated and that the therapeutic methods would be developed. The present study on PNH was only possible using the experimental technique for ferrets developed by the research team. This animal model technique could also contribute to studies of other neurological diseases that have been difficult to investigate with conventional model animals.

Explore further: Researchers discover a gene's key role in building the developing brain's scaffolding

More information: Naoyuki Matsumoto et al, Pathophysiological analyses of periventricular nodular heterotopia using gyrencephalic mammals, Human Molecular Genetics (2017). DOI: 10.1093/hmg/ddx038

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Researchers develop new animal model to study rare brain disease - Medical Xpress

Three women suffering from a degenerative eye condition were blindedlikely permanentlyin a clinical trial for stem cell therapy, according to a report published Wednesday in the New England Journal of Medicine.

The women, who were all between the ages of 72 and 88, had a common medical condition called age-related macular degeneration, in which cells in the retina begin to die off, resulting in spotty or blurred vision. Researchers suspected stem cells derived from the patients own body could regenerate some of the cells lost to the disease. So in the clinical trial, which was conducted in 2015, researchers removed some blood and fat from participants anesthetized abdomens, treated the cells in a standardized way to make them revert to stem cells, then injected into their eyes. They were instructed to use an eyedrops antibiotic for a few days. The three patients had found the trial listed on the government web site clinicaltrials.gov, and had each paid $5,000 for the procedure. The informed consent form listed that blindness was possible as a result of the procedure.

A few days after the patients received the injected stem cells, the participants ended up in the hospital with vision loss, detached retinas, and hemorrhage. The patients lost vision; subsequent checkups led doctors to conclude that they would likely never regain their sight.

Despite the fact that the participants found the procedure on clinicaltrials.gov, the informed consent forms do not mention that it is in fact a clinical trial. The patients paid for a procedure that had never been studied in a clinical trial, lacked sufficient safety data, and was performed in both eyes on the same day, the study authors write. Injecting something experimental into both eyes is both not safe and not typical, they continue.

Recently researchers have been testing lots of different medical uses for stem cells, from treating multiple sclerosis to spinal cord injuries. With the passage of the 21st Century Cures Act in December, Congress cleared the way for faster regulatory approval for promising treatments based on stem cells. At least 13 clinical trials were registered to treat AMD alone as of November 2016, the article authors write.

But anecdotes like these bolster those who counsel restraint when it comes to stem cells. Although numerous stem-cell therapies for medical disorders are being investigated at research institutions with appropriate regulatory oversight, many stem-cell clinics are treating patients with little oversight and with no proof of efficacy, the article authors write.

Jeffrey Goldberg, a professor of ophthalmology at Stanford University and one of the authors of the article, calls this a call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research, according to a press release.

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Three Women Blinded In Stem Cell Clinical Trial - Vocativ

By Isaac GuererroStaff writer

Xue-Jun Li spends her days studying motor neurons, the cells that send signals from the brain to the body's voluntary muscles.

Motor neuron diseases are degenerative, which means that the muscles don't stop working all at once. When the motor neurons begin to fail, one slowly loses control of the arms and legs, the ability to swallow and, eventually, to breathe.

Scientists know very little about the human nervous system and what causes the motor neurons to stop functioning. Li has published more than 37 peer-reviewed manuscripts and has developed human stem cell models for spastic paraplegias and spinal muscular atrophy, which is the leading genetic cause of death for infants.

Li joined the University of Illinois College of Medicine at Rockford as an associate professor in the Biomedical Sciences Department last May. Her research is supported by the National Institute of Health and ALS Association, among others.

I love the satisfaction of new discoveries, new ideas you get from working in the lab, the interaction with students, she said. But any breakthrough you make is a collaboration.

Her stem cell research is concerned with, among other things, an attempt to better understand microtubule defects that disrupt signals from the brain to motor neurons along the spinal cord. Mitochondrial defects the mitochondria are the energy factories of the cells are another focus.

This fall, Li will teach a class that's a first for the university: stem cells and regenerative engineering.

Isaac Guerrero: 815-987-1361; iguerrero@rrstar.com;@isaac_rrs

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Transform 815: Xue Jun-Li's stem cell research in Rockford sheds light on motor neuron diseases - Rockford Register Star

BRUSSELS Belgian biotech group Tigenix said on Monday its medical trial with a novel treatment for patients at risk of heart failure after a coronary attack was successful.

The group said patients treated in its PhaseI/II trial of donor-derived expanded cardiac stem cells (AlloCSC) showed no side-effects and all of them continued to live after 30 days, six months and a year.

Tigenix added that in one subgroup of trial patients associated with a poor long-term outlook, there was a larger reduction in the size of infarction, tissue death due to inadequate blood supply.

"This is the first trial in which it has been demonstrated that allogeneic cardiac stem cells can be transplanted safely through the coronary tree," one of the doctors in the trial said.

The group said it would now analyze the data from the trial and decide on how to proceed with its research.

(Reporting by Robert-Jan Bartunek; editing by Philip Blenkinsop)

LONDON A French biotech firm is hoping to gain approval within months for a nuclear medicine targeting the type of cancer that killed Steve Jobs.

NEW YORK Developers of an experimental blood test for autism say it can detect the condition in more than 96 percent of cases and do so across a broad spectrum of patients, potentially allowing for earlier diagnosis, according to a study released on Thursday.

(Reuters Health) - Getting too little sleep in early childhood is linked to cognitive and behavioral problems years later, a U.S. study suggests.

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Belgium's Tigenix says heart attack stem cell trial successful - Reuters

Scientists at The University of Queensland have taken a significant step forward in cardiac disease research by creating a functional beating human heart muscle from stem cells.

Dr James Hudson and Dr Enzo Porrello from the UQ School of Biomedical Sciences collaborated with German researchers to create models of human heart tissue in the laboratory so they can study cardiac biology and diseases in a dish.

The patented technology enables us to now perform experiments on human heart tissue in the lab, Dr Hudson said.

This provides scientists with viable, functioning human heart muscle to work on, to model disease, screen new drugs and investigate heart repair.

The UQCardiac Regeneration Laboratoryco-leaders have also extended this research and shown that the immature tissues have the capacity to regenerate following injury.

In the laboratory we used dry ice to kill part of the tissue while leaving the surrounding muscle healthy and viable, Dr Hudson said.

We found those tissues fully recovered because they were immature and the cells could regenerate in contrast to what happens normally in the adult heart where you get a dead patch.

Our goal is to use this model to potentially find new therapeutic targets to enhance or induce cardiac regeneration in people with heart failure.

Studying regeneration of these damaged, immature cells will enable us to figure out the biochemical events behind this process.

Hopefully we can determine how to replicate this process in adult hearts for cardiovascular patients.

UQ scientists create beating human heart muscle from The University of Queensland on Vimeo.

Each year, about 54,000 Australians suffer a heart attack, with an average of about 23 deaths every day.

The UQ research has been supported by the National Health and Medical Research Council (NHMRC) and the National Heart Foundation.

Heart Foundation Queensland CEO Stephen Vines said the charity was excited to fund such an important research project.

Heart attack survivors who have had permanent damage to their heart tissue are essentially trying to live on half an engine, Mr Vines said.

The research by Dr Hudson and Dr Porello will help unlock the key to regenerating damaged heart tissue, which will have a huge impact on the quality of life for heart attack survivors.

Dr Hudson and Dr Porello are deserved recipients of our highest national research accolade the Future Leader Fellowship Award.

The research is published in Circulation and Development.

Media: Dr James Hudson, j.hudson@uq.edu.au; Kim Lyell, k.lyell@uq.edu.au, 0427 530 647.

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Scientists create 'beating' human heart muscle for cardiac research - UQ News

A retina with macular degeneration. (Image: University of Iowa)

An unproven stem cell therapy conducted by a Florida clinic has blinded three patients in an apparent clinical trial gone horribly wrong. The incident showcases the extent to which unscrupulous clinics will take advantage of desperate patientsand how the lack of government oversight contributes to the problem.

As reported in the New England Journal of Medicine, the clinical trialif it can be called thatinvolved three women between the ages of 72 and 88 who were suffering from macular degeneration, a common progressive disease of the retina that leads to loss of vision. The women, all of whom were experiencing various degrees of vision loss, sought the help of a Florida clinic, which claimed to be testing a stem cell procedure designed to treat macular degeneration. Sometime in 2015, a week after stem cells were injected into their eyes, the women became blind. Two years later, doctors say theres virtually no chance the womens vision will be restored.

The authors of the new report, ophthalmologists Jeffrey Goldberg from Stanford University School of Medicine and Thomas Albini from the University of Miami, said the unfortunate incident serves as a call to awareness for patients, physicians and regulatory agencies of the risks of this kind of minimally regulated, patient-funded research.

Stem cells are undifferentiated cells that havent quite decided what they want to be when they grow up. Under the right conditions, these immature cells can be transformed into virtually any kind of cell found in the body, which is why theyve proven useful in regenerative medicine.

Eventually, scientists hope to be able to use stem cells to regenerate damaged tissue and organsand possibly even repair the effects of macular degenerationbut were not there yet. The only truly effective clinical application of stem cells to date has been in bone marrow transplants, in which stem cells extracted from a donors bone marrow are used to produce a fresh blood system for patients suffering from blood disorders such as leukemia. A recent study showed that there are nearly 600 clinics peddling unproven stem-cell procedures in the United States for a wide range of conditions, including arthritis, autism, cerebral palsy, stroke, muscular dystrophy, and cancer.

As noted in the NEJM report, two of the three patients learned about the stem cell trial for macular degeneration on ClinicalTrials.gov, a registry run by the US National Library of Medicine. The listings on this site arent fully scrutinized for scientific efficacy. The patients were reportedly under the assumption that they were participating in a bonafide clinical trial, but the consent form and other materials made no mention of a trial. Tellingly, each patient had to pay $5,000 for the procedure. This is highly unorthodox for a clinical trial, and it should have been cause for alarm. Im not aware of any legitimate research, at least in ophthalmology, that is patient-funded, Albini said in a statement.

The NEJM study didnt identify the Florida clinic responsible, but (conveniently) the authors provided the name of the trial: Study to assess the safety and effects of cells injected intravitreal in dry macular. A quick Google search calls the trial up, along with the name of the company responsible: Bioheart Inc., otherwise known as US Stem Cell. As the ClinicalTrials.gov page indicates, the study has been withdrawn prior to enrollment. According to Goldberg and Albini, the company is no longer performing the procedure, but it is still seeing patients.

The trial itself was a joke, lacking in all the components of a properly designed test. It wasnt based on prior laboratory experiments, no control group was assigned, no data was collected, and no plans were made for follow-ups.

During the procedure, the patients had some of their fat cells (i.e. adipose tissue) removed, along with a standard blood withdrawal. The fat tissues were then processed with an enzyme to draw out stem cells. Once plasma was isolated from the blood and added to the stem cells, the mixture was injected into both eyes of each patientyes, both eyes. Again, another serious clinical no-no; normally, only one eye would be injected for an experimental procedure like this in the event that something should go wrong. The entire procedure lasted less than an hour.

A week later, all three women were blind. As noted in the NEJM report, the blindness was accompanied by detached retinas and hemorrhaging.

The patients severe visual loss after the injection was associated with ocular hypertension, hemorrhagic retinopathy, vitreous hemorrhage, combined traction and rhegmatogenous retinal detachment, and lens dislocation. After one year, the patients visual acuity ranged from 20/200 to no light perception.

Goldberg and Albini say the preparation of the stem cells was likely shoddy, and the injections may have been contaminated. Once in the eye, the stem cells could have changed into myofibroblasts, a type of cell associated with scarring.

The Florida clinic, it would appear, was appealing to the desperation of their patients, while taking advantage of a regulatory loophole. As the authors write in their report:

Adipose tissuederived stem cells have been increasingly used by stem-cell clinics because of the relative ease of obtaining and preparing these cells. Many of the clinics that provide these stem-cell therapies have done so under the auspices of patient-funded, institutional review boardapproved research, and the research is listed on ClinicalTrials.gov without an investigational new drug filing with the FDA.

At the time, the procedure was not subject to FDA approval because the cells werent transferred between patients, and because the cells were considered minimally processed. The FDA has since revised its requirements, and it now needs approval for these types of procedures. In addition to updating its regulations, the FDA is also clamping down on stem cell clinics.

Thats obviously a good thing, but its a little too late for the women involved. This incident shows what happens when regulations and oversight are weak, and how shady companies will take risks with their patients health. Certainly food for thought as Trump and his cronies start to recreate the FDA in their own image.

Update: We reached out to US Stem Cell Clinic for comment and they responded with this statement:

Founded in 1999, U.S Stem Cell, Inc. has been committed to the research and development of effective cell technologies to treat patients with a variety of diseases and injuries. Since 2001, our clinics have successfully conducted more than 7,000 stem cell procedures with less than 0.01% adverse reactions reported. We are unable to comment further on specific cases due to patient confidentiality or legal confidentiality obligations. Neither US Stem Cell nor US Stem Cell Clinic currently treats eye patients.

[New England Journal of Medicine]

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Florida Clinic Blinds Three Patients in Botched 'Clinical Trial' - Gizmodo

For Release: March 15, 2017 Contact: Grove Potter, mpotter3@buffalo.edu University at Buffalo 716-645-2130 From skin to brain: Stem cells without genetic modification

UB study yields neural crest cells from adult skin cells, and could lead to new treatments for Parkinsons and other brain illnesses

BUFFALO, N.Y. A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain.

The applications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patients own cells.

Its actually quite remarkable that it happens, says Stelios T. Andreadis, PhD, professor and chair of UBs Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.

The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

In medical applications this has tremendous potential because you can always get a skin biopsy, Andreadis says. We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources.

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis says, as successive experiments kept leading to something new. It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition, Andreadis says. Collaborators include Gabriella Popescu, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UBs School of Public Health and Health Professions; and Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology.

Andreadis credits the persistence of his then-PhD student, Vivek K. Bajpai, for sticking with it.

He is an excellent and persistent student, Andreadis says. Most students would have given up. Andreadis also credits a seed grant from UBs office of the Vice President for Research and Economic Developments IMPACT program that enabled part of the work. The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinsons-like symptoms in a mouse model of hypomyelinating disease. This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further, Andreadis said.

The research, described in the journal Stem Cells under the title Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates, was supported by grants from the National Institutes of Health.

SEE ORIGINAL STUDY

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From Skin to Brain: Stem Cells Without Genetic Modification

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain.

The practical implications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patient's own cells.

"It's actually quite remarkable that it happens," said Stelios T. Andreadis, Ph.D., professor and chair of UB's Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.

The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

"In medical applications this has tremendous potential because you can always get a skin biopsy," Andreadis said. "We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources."

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis said, as successive experiments kept leading to something new. "It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition," Andreadis said. Collaborators include Gabriella Popescu, Ph.D., professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, Ph.D., vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UB's School of Public Health and Health Professions; and Marianne Bronner, Ph.D., professor of biology and biological engineering, California Institute of Technology.

Andreadis credits the persistence of his then-Ph.D. student, Vivek K. Bajpai, for sticking with it.

"He is an excellent and persistent student," Andreadis said. "Most students would have given up." Andreadis also credits a seed grant from UB's office of the Vice President for Research and Economic Development's IMPACT program that enabled part of the work.

The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinson's-like symptoms in a mouse model of hypomyelinating disease.

"This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further," Andreadis said.

See original here:
From Skin to Brain: Stem Cells Without Genetic Modification - Bioscience Technology

Studying brain disorders is complicated for many reasons, not the least being the ethics of obtaining living neurons. To overcome that obstacle, UC San Francisco postdoc Aditi Deshpande, PhD, is starting with skin cells.

Thanks to developments in stem cell technology, new information about the human brain is now being gleaned from a simple cheek swab or skin sample. This technology is key to the kind of progress Despande and researchers like her are making. It allows them to work with cells otherwise unobtainable living brain cells that have the same genetics as the patients.

Deshpande begins with skin cells obtained from the Simons Foundation from volunteers whose DNA contains a specific deletion or duplication of one chromosome. She cultures these cells and then turns them into induced pluripotent stem cells cells that have been coaxed back to their embryonic state and are able to become any other type of cell. From there, she reprograms them to become a specific type of neuron thats involved in attention and information processing.

The deletion or duplication Deshpande is looking for stems from a 2008 finding by Lauren Weiss, PhD, an associate professor of neurology in the UCSF Department of Psychiatry and the UCSF Institute for Human Genetics.

Weiss discovered a 29-gene region of DNA on chromosome 16 that is associated with autism, seizures and other brain disorders. Normally, a person has two copies of the region one on each copy of chromosome 16. In some of Deshpandes samples, the region is deleted from one chromosome, leaving one copy. In others, the region is duplicated, resulting in three copies. Subjects with only one copy of the region were more likely to have macrocephaly an enlarged brain than a typical subject, and those with three copies were more likely to have microcephaly a smaller brain.

Whats really interesting, said Deshpande, is that although these subjects seem to have opposite features in terms of brain size, we see a related effect, based on whether they have fewer or more copies of the region.

Some known models of autism show a connection between a neurons growth or appearance and macrocephaly, she explained. We wanted to know if the same thing is happening here.

To compare the effect of the mutation, Deshpande first stains the obtained skin cells so that she can visualize the neurons under a microscope. After staining, Deshpande used cell-counting software to assess several thousands of neurons from deletion and duplication samples and measure them against normal neurons. She found that the neurons missing the DNA region exhibited some differences compared to typical neurons.

Her next step in her research is to discern which of the regions 29 genes are involved in these differences.

The work is meticulous, but Deshpande doesnt mind. I simply love looking at neurons, she said. It really makes you appreciate the complexity of the brain.

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Science in Focus: Creating Neurons from Skin Cells to Understand Autism - UCSF News Services

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Some genetic variations difficult to evaluate using current stem cell modeling techniques Science Daily Stem cell-based disease modeling involves taking cells from patients, such as skin cells, and introducing genes that reprogram the cells into human-induced pluripotent stem cells (hiPSCs). These "master cells" are unspecialized, meaning they can be ... Would You Slather Blood and Breast Milk on Your Face?Racked all 19 news articles »

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Some genetic variations difficult to evaluate using current stem cell modeling techniques - Science Daily

Scientists have long hoped that stem cells might have the power to treat diseases. But it's always been clear that they could be dangerous too, especially if they're not used carefully.

Now a pair of papers published Wednesday in the New England Journal of Medicine is underscoring both the promise and the peril of using stem cells for therapy.

In one report, researchers document the cases of three elderly women who were blinded after getting stem cells derived from fat tissue at a for-profit clinic in Florida. The treatment was marketed as a treatment for macular degeneration, the most common cause of blindness among the elderly. Each woman got cells injected into both eyes.

In a second report, a patient suffering from the same condition had a halt in the inexorable loss of vision patients usually experience, which may or may not have been related to the treatment. That patient got a different kind of stem cell derived from skin cells as part of a carefully designed Japanese study.

The Japanese case marks the first time anyone has given induced pluripotent stem (iPS) cells to a patient to treat any condition.

"These two reports are about as stark a contrast as it gets," says George Q. Daley, Harvard Medical School's dean and a leading stem cell researcher. He wrote an editorial accompanying the two papers. "It's really striking."

The report about the three women in their 70s and 80s who were blinded in Florida is renewing calls for the Food and Drug Administration to crack down on the hundreds of clinics that are selling unproven stem cell treatments for a wide variety of medical conditions, including arthritis, autism and stroke.

"One of the big mysteries about this particular case and the mushrooming stem cell clinic industry more generally is why the FDA has chosen to effectively sit itself out on the sidelines even as this situation overall grows increasingly risky to patients," says Paul Knoepfler, a University of California, Davis, stem cell researcher who has studied the proliferation of stem cell clinics.

"The inaction by the FDA not only puts many patients at serious risk from unproven stem cell offerings, but also it undermines the agency's credibility," Knoepfler wrote in an email.

In response to a query from Shots, an FDA spokeswoman wrote in an email that the agency is in the process of finalizing four new guidelines aimed at clarifying how clinics could use stem cells as treatments. The agency also noted that it had previously issued a warning to patients.

In the meantime, "consumers are encouraged to contact FDA and the appropriate state authorities in their jurisdictions to report any potentially illegal or harmful activity related to stem cell based products," the FDA email says.

Other researchers say the cases should stand as a warning to patients considering unproved stem cell treatments, especially those tried outside carefully designed research studies.

"Patients have to be wary and tell the difference between the snake oil salesmen who are going to exploit them and the kind of slow, painstaking legitimate clinical trials that are also going on," Daley says.

The New England Journal of Medicine report did not name the Florida clinic, but noted that the treatment was listed on a government website that serves as a clearinghouse for research studies. The sponsor is listed as Bioheart, Inc., which is part of U.S. Stem Cell Inc. in Sunrise, Fla.

Kristen Comella, the scientific director of U.S. Stem Cell, would not discuss the cases. "There were legal cases associated with eye patients that were settled under confidentiality, so I am not permitted to speak on any details of those cases due to the confidentiality clause," Comella said by phone.

She acknowledged, however, that the clinic had been performing the stem cell procedures. They were discontinued after at least two patients suffered detached retinas, she says.

But Comella defended the use of stem cells from fat tissue to treat a wide variety of other health problems.

"We have treated more than 7,000 patients and we've have had very few adverse events reported. So the safety track record is very strong," Comella says. "We feel very confident about the procedures that we do, and we've had great success in many different indications."

According to the New England Journal of Medicine report, The Florida clinic was using adult stem cells, which circulate in various parts of the body, including in fat tissue. While those cells may someday be turn out to be useful for treating disease, none have been proven to work.

The body produces a variety of stem cells. The kind that have generated the most excitement and controversy are human embryonic stem cells, which are derived from early human embryos and can be coaxed to become any kind of cell in the body.

Scientists are also excited about iPS cells, which can be made in the laboratory by turning any cell in the body, such as skin cells, into cells that resemble embryonic stem cells.

Those are the cells that were tested by the Japanese scientists. The stem cells were converted into retinal pigment epithelium (RPE) cells, which are the cells that are destroyed by macular degeneration.

"This represents a landmark," says Daley. "It's the first time any patient has been treated with cellular derivatives of iPS cells. So it's definitely a world first."

Daley noted that the scientists only treated one of the patient's eyes in case something went wrong, to ensure remaining vision would not be threatened in the other eye.

After at least a year, no complications had occurred and the patient had not experienced any further deterioration of vision in the treated eye. While that is promising, more patients would have to be treated and followed for much longer to know whether that approach is successful, Daley says.

"Given that macular degeneration is the most frequent cause of vision loss and blindness in the elderly and our population is aging, the prevalence of macular degeneration is going up dramatically," Daley says. "So to be able to preserve or even restore sight would be a really remarkable medical advance."

Despite the potentially encouraging results with the first patient, Daley noted that the Japanese scientists decided not to treat a second patient and suspended the study. That's because they discovered worrisome genetic variations in the RPE cells they had produced for the second patient.

"They weren't certain these would cause problems for the patient, but they were restrained enough and cautious enough that they decided not to go forward," Daley says. "That's what contrasts so markedly with the approach of the second group, who treated the three patients with an unproven stem cell therapy that ended up have devastating effects on their vision."

In this case, the New England Journal of Medicine report says, patients paid $5,000 each to receive injections of solutions that supposedly contained stem cells that were obtained from fat removed from their abdomens through liposuction.

Even though the safety and effectiveness of this procedure is unknown, all three patients received injections in both eyes.

"That's what led to these horrible results," says Thomas Albini, a retina specialist at the University of Miami's Bascom Palmer Eye Institute, who helped write the report.

Before the procedure, all three women still had at least some vision. Afterwards, one woman was left completely blind while the other two were effectively blind, Albini and his colleagues reported.

The cases show that patients need to be warned that something that "sounds too good to be true may indeed be too good to be true and may even be horrible," Albini says.

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3 Women Blinded By Unproven Stem Cell Treatments - NPR

Monday, March 13, 2017 3 a.m. CDT

BRUSSELS (Reuters) - Belgian biotech group Tigenix said on Monday its medical trial with a novel treatment for patients at risk of heart failure after a coronary attack was successful.

The group said patients treated in its PhaseI/II trial of donor-derived expanded cardiac stem cells (AlloCSC) showed no side-effects and all of them continued to live after 30 days, six months and a year.

Tigenix added that in one subgroup of trial patients associated with a poor long-term outlook, there was a larger reduction in the size of infarction, tissue death due to inadequate blood supply.

"This is the first trial in which it has been demonstrated that allogeneic cardiac stem cells can be transplanted safely through the coronary tree," one of the doctors in the trial said.

The group said it would now analyze the data from the trial and decide on how to proceed with its research.

(Reporting by Robert-Jan Bartunek; editing by Philip Blenkinsop)

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Belgium's Tigenix says heart attack stem cell trial successful - KFGO

Runner's World

Stem Cell Therapy Runner's World This is why researchers and physicians think this therapy may help joint injuries caused by worn-out cartilage; in cell cultures, stem cells can grow new cartilage, and if this can happen in a joint, it may prevent the need for a joint replacement ... Nutrients Boost Stem Cell FunctionProHealth all 19 news articles »

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Stem Cell Therapy - Runner's World

"The impact of Alzheimer's disease is vast, far exceeding the medical community's current ability to treat it," said Joshua M. Hare, M.D., Longeveron's Co-Founder and Chief Science Officer. "Regenerative medicine and cell-based therapies offer a promising new approach to close this gap and address the urgent need for effective therapies to combat the condition."

An important component in the progression of Alzheimer's disease is neuroinflammation. Longeveron was recently awarded a $1 million Part the Cloud Challenge on Neuroinflammation grant from the Alzheimer's Association to help support this research.

"Adult stem cells are very potent anti-inflammatories. The characteristic amyloid plaques found in the brains of Alzheimer's disease patients produce inflammation, and stem cells can reduce inflammation," explained Bernard S. Baumel, M.D., Principal Investigator for the trial. "Alzheimer's also impairs the brain's ability to adequately produce new brain cells in the memory area known as the hippocampus. Stem cells can stimulate the brain to produce these new cells needed to form memory. We believe that an infusion of LMSCs may improve the condition or at least halt the progression of the disease."

Prior research shows that adult MSCs target and reduce inflammation, promote tissue repair and improve brain function in mouse models of Alzheimer's disease. Longeveron's trial is the first U.S. clinical study of exogenously administered mesenchymal stem cells derived from the bone marrow of healthy adult donors for treating Alzheimer's disease.

To learn about participating in the clinical trial, visit: https://clinicaltrials.gov/ct2/show/NCT02600130

About Longeveron

Longeveron is a regenerative medicine therapy company founded in 2014. Longeveron's goal is to provide the first of its kind biological solution for aging-related diseases, and is dedicated to developing safe cell-based therapeutics to revolutionize the aging process and improve quality of life. The company's research focus areas include Alzheimer's disease, Aging Frailty and the Metabolic Syndrome. Longeveron produces LMSCs in its own state-of-the-art cGMP cell processing facility. http://www.longeveron.com

Contact: Suzanne Liv Page spage@longeveron.com 305.342.9590

To view the original version on PR Newswire, visit:http://www.prnewswire.com/news-releases/longeveron-achieves-milestone-in-groundbreaking-stem-cell-trial-for-alzheimers-disease-300424206.html

SOURCE Longeveron

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Longeveron Achieves Milestone in Groundbreaking Stem Cell Trial for Alzheimer's Disease - PR Newswire (press release)

Adam Krief, with his wife, Lia, had a rare form of blood cancer that proved to be fatal. (Facebook)

(JTA) Adam Krief, a Jewish cancer patient whose search for a bone marrow donor captured the attention of social media and celebrities including Kim Kardashian, Mayim Bialik and Jason Biggs, has died.

Krief, a father of three from Los Angeles, died Tuesday, a family friend confirmed to JTA. He was 32.

Krief was diagnosed with primary myelofibrosis, a rare form of blood cancer that is likely fatal if a stem celltransplant matchis notfound.To find anHLA, or gene complex matchfor Krief something more difficultto track downthan a blood type match drives were held around the world, including in North America,Israel, France and Mexico.

Kardashian posted about Krief on Facebook in September, saying he was a friend of a friend.

A bone-marrow donor was found last December seven matches were found, in fact, through the donor drives organized for him.

This is what cloud 9 looks like Im so grateful to let you all know that a donorhas been found, Krief wrote at the time, sharing a video with two of his children.

The Hope 4 Adam Facebook page on March 8 called for a Worldwide Unity Shabbat for March 11 and March 18 for the recovery of Krief, asking followers to Help us bring about a miracle.

On Monday, the Eretz Kabbalah Facebook page of the Los Angeles-based Eretz Cultural Center posted a call for followers to recite Tehillim, or psalms, on behalf of Krief.

After a long search for a bone-marrow match to save his life, he finally received one. However, after some complications, he is said to only have a few hours to live, the post said.

Krief is survived by his wife, Lia, and his young children.

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Jewish cancer patient finds bone marrow transplant following worldwide search, Kim Kardashians pitch

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Adam Krief, Jewish father of 3 whose bone marrow search inspired celebrities, dies - Jewish Telegraphic Agency

A longtime product developer is bringing a peptide ingredient to the US market that has been researched for a unique property promoting the growth of bone marrow stem cells.

Called DH Stemogen, the product is the brainchild of Dr Marvin Heuer MD who has a history of product development with sports nutrition company MuscleTech. Dr. Heuer has a background in clinical research, having spent many years in drug development at Glaxo Smith Kline. He also runs a contract research firm, Heuer M.D. Research Inc. and is the CEO of omega-3 supplement manufacturer Blue Ocean Nutrascience.

The new product, called DH Stemogen is based on a Cyclo-{L-ALA-L-GLU(TRP-OH) peptide that was developed by a Russian biochemist.

Its a peptide that is a mimic of a naturally occurring thymic peptide,Dr. Heuer told NutraIngredients-USA. Heuer was promoting the launch of the product at the recent Expo West trade show in Anaheim, CA. At Heuer M.D. Research, as a company we are out looking for novel ingredientsto bring out, hopefully in the nutraceutical area.

We got interested in Prof. Vlad Deigins peptide research, Dr. Heuer said (Deigin is associated with the Institute of Bioorganic Chemistry at the Russian Academy of Sciences in Moscow.)We looked at this particular compound that he was launching as an ingredient in Russia about a year ago.

The peptide in DH Stemogen targets a particular type of stem cell hematopoietic cells (HSC). Stem cells in general are the building blocks of our bodies. These cells are able to transform themselves into almost any type of cell. There are various sources of stem cells in an adult body. One of the most important of them comprises the bone marrow, where the HSCs are produced. HSCs transform into all the main cell types in our blood, including red blood cells and white blood cells. Dr. Heuer said there is some evidence that those cells are able to reconstruct other body tissues by transforming into the specific tissue type cell such as liver, nervous tissue, kidney and skin.

These properties would seem to make Stemogen a natural for a healthy aging product positioning, Dr. Heuer said. But Deigins research, trending as it does over into disease endpoints, is a little problematical when it comes to supporting US-style structure function claims, he admitted. Other countries dont make the same hard and fast distinctions between dietary ingredients meant for supplement applications and active pharmaceutical agents meant for drugs, he said.

We are going to be very cautious about making structure/function claims,Dr. Heuer said. The product at the moment saysSupport your immune system and Support healthy levels of stem cells in your blood.

We are about to begin a whole profile of research in the U.S. and Canada, he added.

Dr. Heuer said one thing thats unique about the ingredient (and something that he says Deigin has patented) is a structural twist that improves the peptides stability. The criticism of some other novel peptides has been that interesting as their properties might be, once they hit the stomachs gastric fluid they blow apart into their constituent amino groups and all those novel properties are lost.

He has a patent on the way he makes this with a hex ring on the end that protects it in the GI tract and allows it to be absorbed,he said.

Bringing a synthetic analogue of a naturally occurring peptide to market as a dietary ingredient would seem to pose significant regulatory challenges. Dr. Heuer said hes confident there is a way through that thicket. The plan is to start first with a GRAS filing, and Dr. Heuer said he believes that the peptide would fall under the amino acid category in the DHSEA definitions of what constitutes a dietary ingredient.

Certainly there is a precedent of complex peptides being sold on the market, he said.

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Peptide aimed at stem cell genesis debuts on supplement market - NutraIngredients-usa.com

Adam Krief, a Jewish cancer patient whose search for a bone marrow donor captured the attention of social media and celebrities including Kim Kardashian, Mayim Bialik and Jason Biggs, has died.

Krief, a father of three from Los Angeles, died Tuesday, a family friend confirmed to JTA. He was 31.

Krief was diagnosed with primary myelofibrosis, a rare form of blood cancer that is likely fatal if a stem cell transplant match is not found. To find an HLA, or gene complex match for Krief something more difficult to track down than a blood type match drives were held around the world, including in North America, Israel, France and Mexico.

Kardashian posted about Krief on Facebook in September, saying he was a friend of a friend.

A bone-marrow donor was found last December seven matches were found, in fact, through the donor drives organized for him.

This is what cloud 9 looks like Im so grateful to let you all know that a donor has been found, Krief wrote at the time, sharing a video with two of his children.

The Hope 4 Adam Facebook page on March 8 called for a Worldwide Unity Shabbat for March 11 and March 18 for the recovery of Krief, asking followers to Help us bring about a miracle.

On Monday, the Eretz Kabbalah Facebook page of the Los Angeles-based Eretz Cultural Center posted a call for followers to recite Tehillim, or psalms, on behalf of Krief.

After a long search for a bone-marrow match to save his life, he finally received one. However, after some complications, he is said to only have a few hours to live, the post said.

Krief is survived by his wife, Lia, and his young children.

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American Jewish father of 3 whose bone marrow search inspired celebrities dies - Jerusalem Post Israel News

The first new finding is an obvious onethe mouse experiments worked in human cells. Just because something worked in mice doesn't necessarily mean it will work in people too. So this is a really important finding.

The second important finding has to do with the specific genes each group used. Both groups added four genes to turn a stem cell into an ES cell. But they used a slightly different set of genes.

The Japanese group added OCT3/4, SOX2, KLF4, and c-MYC. The Wisconsin group added OCT4, SOX2, NANOG, and LIN28. This matters because of a side effect seen in the previous mouse study.

The mouse study went farther than the human study in that the researchers added these new ES cells to a mouse embryo. The results were disconcerting. Around 20% of the mice developed cancer from the cells. The researchers hypothesized that the cause was one or more of the genes that were used to create the ES cell.

By using different sets of genes in the human cell study, the researchers showed you don't need the same four genes to create an ES cell. The hope is that the researchers will find a combination of genes that do not cause cancer.

Once the scientists find a set of genes that don't cause cancer, this research should blow the stem cell field wide open. We still don't know if ES cells will work to actually cure disease. But ethical ES cells should open the spigot of federal funds so American scientists can finally research this subject to its full extent. Then we'll see if ES cells can really live up to their hype. Or if we need to pursue other ways to cure these illnesses.

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Human Embryonic Stem (ES) Cells from Skin Cells ...

March 15, 2017 by Grove Potter The four images, from left to right, show Keratinocyte-derive neural crest stem cells turning into neurons as shown by typical neuronal morphology. Credit: University at Buffalo.

A discovery, several years in the making, by a University at Buffalo research team has proven that adult skin cells can be converted into neural crest cells (a type of stem cell) without any genetic modification, and that these stem cells can yield other cells that are present in the spinal cord and the brain.

The practical implications could be very significant, from studying genetic diseases in a dish to generating possible regenerative cures from the patient's own cells.

"It's actually quite remarkable that it happens," says Stelios T. Andreadis, PhD, professor and chair of UB's Department of Chemical and Biological Engineering, who recently published a paper on the results in the journal Stem Cells.

The identity of the cells was further confirmed by lineage tracing experiments, where the reprogrammed cells were implanted in chicken embryos and acted just as neural crest cells do.

Stem cells have been derived from adult cells before, but not without adding genes to alter the cells. The new process yields neural crest cells without addition of foreign genetic material. The reprogrammed neural crest cells can become smooth muscle cells, melanocytes, Schwann cells or neurons.

"In medical applications this has tremendous potential because you can always get a skin biopsy," Andreadis says. "We can grow the cells to large numbers and reprogram them, without genetic modification. So, autologous cells derived from the patient can be used to treat devastating neurogenic diseases that are currently hampered by the lack of easily accessible cell sources."

The process can also be used to model disease. Skin cells from a person with a genetic disease of the nervous system can be reprogrammed into neural crest cells. These cells will have the disease-causing mutation in their chromosomes, but the genes that cause the mutation are not expressed in the skin. The genes are likely to be expressed when cells differentiate into neural crest lineages, such as neurons or Schwann cells, thereby enabling researchers to study the disease in a dish. This is similar to induced pluripotent stem cells, but without genetic modification or reprograming to the pluripotent state.

The discovery was a gradual process, Andreadis says, as successive experiments kept leading to something new. "It was one step at a time. It was a very challenging task that took almost five years and involved a wide range of expertise and collaborators to bring it to fruition," Andreadis says. Collaborators include Gabriella Popescu, PhD, professor in the Department of Biochemistry in the Jacobs School of Medicine and Biomedical Sciences at UB; Song Liu, PhD, vice chair of biostatistics and bioinformatics at Roswell Park Cancer Institute and a research associate professor in biostatistics UB's School of Public Health and Health Professions; and Marianne Bronner, PhD, professor of biology and biological engineering, California Institute of Technology.

Andreadis credits the persistence of his then-PhD student, Vivek K. Bajpai, for sticking with it.

"He is an excellent and persistent student," Andreadis says. "Most students would have given up." Andreadis also credits a seed grant from UB's office of the Vice President for Research and Economic Development's IMPACT program that enabled part of the work.

The work recently received a $1.7 million National Institutes of Health grant to delve into the mechanisms that occur as the cells reprogram, and to employ the cells for treating the Parkinson's-like symptoms in a mouse model of hypomyelinating disease.

"This work has the potential to provide a novel source of abundant, easily accessible and autologous cells for treatment of devastating neurodegenerative diseases. We are excited about this discovery and its potential impact and are grateful to NIH for the opportunity to pursue it further," Andreadis said.

The research is described in the journal Stem Cells under the title "Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates."

Explore further: Embryonic gene Nanog reverses aging in adult stem cells

More information: Vivek K. Bajpai et al, Reprogramming Postnatal Human Epidermal Keratinocytes Toward Functional Neural Crest Fates, STEM CELLS (2017). DOI: 10.1002/stem.2583

Journal reference: Stem Cells

Provided by: University at Buffalo

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From skin to brain: Stem cells without genetic modification - Phys.Org