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Category Archives: Stem Cell Research

UCLA scientists identify a new way to activate stem cells to make hair grow – UCLA Newsroom

Posted: August 15, 2017 at 1:42 pm

UCLA researchers have discovered a new way to activate the stem cells in the hair follicle to make hair grow. The research, led by scientists Heather Christofk and William Lowry, may lead to new drugs that could promote hair growth for people with baldness or alopecia, which is hair loss associated with such factors as hormonal imbalance, stress, aging or chemotherapy treatment.

The research was published in the journal Nature Cell Biology.

Hair follicle stem cells are long-lived cells in the hair follicle; they are present in the skin and produce hair throughout a persons lifetime. They are quiescent, meaning they are normally inactive, but they quickly activate during a new hair cycle, which is when new hair growth occurs. The quiescence of hair follicle stem cells is regulated by many factors. In certain cases they fail to activate, which is what causes hair loss.

In this study, Christofk and Lowry, of Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, found that hair follicle stem cell metabolism is different from other cells of the skin. Cellular metabolism involves the breakdown of the nutrients needed for cells to divide, make energy and respond to their environment. The process of metabolism uses enzymes that alter these nutrients to produce metabolites. As hair follicle stem cells consume the nutrient glucose a form of sugar from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate. The cells then can either send pyruvate to their mitochondria the part of the cell that creates energy or can convert pyruvate into another metabolite called lactate.

Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, said Christofk, an associate professor of biological chemistry and molecular and medical pharmacology.

The research team first blocked the production of lactate genetically in mice and showed that this prevented hair follicle stem cell activation. Conversely, in collaboration with the Rutter lab at University of Utah, they increased lactate production genetically in the mice and this accelerated hair follicle stem cell activation, increasing the hair cycle.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, said Lowry, a professor of molecular, cell and developmental biology. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

The team identified two drugs that, when applied to the skin of mice, influenced hair follicle stem cells in distinct ways to promote lactate production. The first drug, called RCGD423, activates a cellular signaling pathway called JAK-Stat, which transmits information from outside the cell to the nucleus of the cell. The research showed that JAK-Stat activation leads to the increased production of lactate and this in turn drives hair follicle stem cell activation and quicker hair growth. The other drug, called UK5099, blocks pyruvate from entering the mitochondria, which forces the production of lactate in the hair follicle stem cells and accelerates hair growth in mice.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, said Aimee Flores, a predoctoral trainee in Lowrys lab and first author of the study. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss. I think weve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; Im looking forward to the potential application of these new findings for hair loss and beyond.

The use of RCGD423 to promote hair growth is covered by a provisional patent application filed by the UCLA Technology Development Group on behalf of UC Regents. The use of UK5099 to promote hair growth is covered by a separate provisional patent filed by the UCLA Technology Development Group on behalf of UC Regents, with Lowry and Christofk as inventors.

The experimental drugs described above were used in preclinical tests only and have not been tested in humans or approved by the Food and Drug Administration as safe and effective for use in humans.

The research was supported by a California Institute for Regenerative Medicine training grant, a New Idea Award from the Leukemia and Lymphoma Society, the National Cancer Institute (R25T CA098010), the National Institute of General Medical Sciences (R01-GM081686 and R01-GM0866465), the National Institutes of Health (RO1GM094232), an American Cancer Society Research Scholar Grant (RSG-16-111-01-MPC), the National Institute of Arthritis and Musculoskeletal and Skin Diseases (5R01AR57409), a Rose Hills Foundation Research Award and the Gaba Fund. The Rose Hills award and the Gaba Fund are administered through the UCLA Broad Stem Cell Research Center.

Further research on the use of UK5099 is being funded by the UCLA Technology Development Group through funds from California State Assembly Bill 2664.

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Cardiac stem cells rejuvenate rats’ aging hearts, study says – CNN – CNN

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The old rats appeared newly invigorated after receiving their injections. As hoped, the cardiac stem cells improved heart function yet also provided additional benefits. The rats’ fur fur, shaved for surgery, grew back more quickly than expected, and their chromosomal telomeres, which commonly shrink with age, lengthened.

The old rats receiving the cardiac stem cells also had increased stamina overall, exercising more than before the infusion.

“It’s extremely exciting,” said Dr. Eduardo Marbn, primary investigator on the research and director of the Cedars-Sinai Heart Institute. Witnessing “the systemic rejuvenating effects,” he said, “it’s kind of like an unexpected fountain of youth.”

“We’ve been studying new forms of cell therapy for the heart for some 12 years now,” Marbn said.

Some of this research has focused on cardiosphere-derived cells.

“They’re progenitor cells from the heart itself,” Marbn said. Progenitor cells are generated from stem cells and share some, but not all, of the same properties. For instance, they can differentiate into more than one kind of cell like stem cells, but unlike stem cells, progenitor cells cannot divide and reproduce indefinitely.

Since heart failure with preserved ejection fraction is similar to aging, Marbn decided to experiment on old rats, ones that suffered from a type of heart problem “that’s very typical of what we find in older human beings: The heart’s stiff, and it doesn’t relax right, and it causes fluid to back up some,” Marbn explained.

He and his team injected cardiosphere-derived cells from newborn rats into the hearts of 22-month-old rats — that’s elderly for a rat. Similar old rats received a placebo injection of saline solution. Then, Marbn and his team compared both groups to young rats that were 4 months old. After a month, they compared the rats again.

Even though the cells were injected into the heart, their effects were noticeable throughout the body, Marbn said

“The animals could exercise further than they could before by about 20%, and one of the most striking things, especially for me (because I’m kind of losing my hair) the animals … regrew their fur a lot better after they’d gotten cells” compared with the placebo rats, Marbn said.

The rats that received cardiosphere-derived cells also experienced improved heart function and showed longer heart cell telomeres.

Why did it work?

The working hypothesis is that the cells secrete exosomes, tiny vesicles that “contain a lot of nucleic acids, things like RNA, that can change patterns of the way the tissue responds to injury and the way genes are expressed in the tissue,” Marbn said.

It is the exosomes that act on the heart and make it better as well as mediating long-distance effects on exercise capacity and hair regrowth, he explained.

Looking to the future, Marbn said he’s begun to explore delivering the cardiac stem cells intravenously in a simple infusion — instead of injecting them directly into the heart, which would be a complex procedure for a human patient — and seeing whether the same beneficial effects occur.

Dr. Gary Gerstenblith, a professor of medicine in the cardiology division of Johns Hopkins Medicine, said the new study is “very comprehensive.”

“Striking benefits are demonstrated not only from a cardiac perspective but across multiple organ systems,” said Gerstenblith, who did not contribute to the new research. “The results suggest that stem cell therapies should be studied as an additional therapeutic option in the treatment of cardiac and other diseases common in the elderly.”

Todd Herron, director of the University of Michigan Frankel Cardiovascular Center’s Cardiovascular Regeneration Core Laboratory, said Marbn, with his previous work with cardiac stem cells, has “led the field in this area.”

“The novelty of this bit of work is, they started to look at more precise molecular mechanisms to explain the phenomenon they’ve seen in the past,” said Herron, who played no role in the new research.

One strength of the approach here is that the researchers have taken cells “from the organ that they want to rejuvenate, so that makes it likely that the cells stay there in that tissue,” Herron said.

He believes that more extensive study, beginning with larger animals and including long-term followup, is needed before this technique could be used in humans.

“We need to make sure there’s no harm being done,” Herron said, adding that extending the lifetime and improving quality of life amounts to “a tradeoff between the potential risk and the potential good that can be done.”

Capicor hasn’t announced any plans to do studies in aging, but the possibility exists.

After all, the cells have been proven “completely safe” in “over 100 human patients,” so it would be possible to fast-track them into the clinic, Marbn explained: “I can’t tell you that there are any plans to do that, but it could easily be done from a safety viewpoint.”

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Researchers Discover New Key to Hair Growth – R & D Magazine

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New drugs promoting hair growth may soon be on the market, as researchers from UCLA have developed a new way to activate the stem cells in the hair follicle to make hair grow.

Hair follicle stem cells are long-lived cells in the hair follicle that are present in the skin and produce hair throughout a persons lifetime. The stem cells are normally inactive, but can quickly activate during a new hair cycle when growth occurs.

The researchers discovered that the hair follicle stem cell metabolism is different from other cells of the skin.

The metabolism uses enzymes that alter nutrients to produce metabolites, and as hair follicle stem cells consume glucose from the bloodstream, they process the glucose to eventually produce a metabolite called pyruvate.

The cells then can either send pyruvate to their mitochondriathe part of the cell that creates energy or they can convert pyruvate into another metabolite called lactate.

Our observations about hair follicle stem cell metabolism prompted us to examine whether genetically diminishing the entry of pyruvate into the mitochondria would force hair follicle stem cells to make more lactate, and if that would activate the cells and grow hair more quickly, Heather Christofk, a scientist at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, said in a statement.

The researchers blocked the production of lactate genetically in mice and found that the hair follicle stem cell was prevented from activating.

They then collaborated with researchers from the University of Utah and increased lactate production genetically in the mice to accelerate hair follicle stem cell activation and ultimately increasing the hair cycle.

Before this, no one knew that increasing or decreasing the lactate would have an effect on hair follicle stem cells, William Lowry, a professor of molecular, cell and developmental biology at UCLA, said in a statement. Once we saw how altering lactate production in the mice influenced hair growth, it led us to look for potential drugs that could be applied to the skin and have the same effect.

A pair of drugs have already been identified and tested. When the drugsRCGD423 and UK5099were applied to the skin of mice they influenced hair follicle stem cells in distinct ways to promote lactate production.

RCGD423 activates the JAK-Stat cellular signaling pathway, which transmits information from outside the cell to the nucleus of the cell and leads to the increased production of lactate, which drives hair follicle stem cell activation and quicker hair growth.

UK5099 blocks pyruvate from entering the mitochondria, forcing the production of lactate in the hair follicle stem cells and accelerating hair growth in mice.

Through this study, we gained a lot of interesting insight into new ways to activate stem cells, Aimee Flores, a predoctoral trainee in Lowry’s lab and first author of the study, said in a statement. The idea of using drugs to stimulate hair growth through hair follicle stem cells is very promising given how many millions of people, both men and women, deal with hair loss.

I think we’ve only just begun to understand the critical role metabolism plays in hair growth and stem cells in general; I’m looking forward to the potential application of these new findings for hair loss and beyond.

The study was published in Nature Cell Biology.

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Stimulating Stem Cells to Encourage Hair Growth – Anti Aging News

Posted: at 1:42 pm

Scientists have discovered a new way to stimulate the stem cells in the hair follicle to make hair grow, opening the door to the development of new drugs for those with baldness or alopecia.

UCLA researchers have revealed a new way to activate stem cells within hair follicles that stimulate hair growth. The hope is this discovery will lead the way to the development of drugs that allow bald individuals and those with alopecia to once again grow hair. The research was led by scientists William Lowry and Heather Christofk of UCLA’s Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research. The details of theirfindings were recently published in Nature Cell Biology.

About Hair Follicle Stem Cells

Hair follicle stem cells are best described simply as older cells within hair follicles that are present in human skin. They generate hair across an individual’s lifetime. These cells are quiescent, meaning they are typically dormant yet they can activate quite rapidly in a new hair cycle when the growth of new hair occurs. The hair follicle stem cells’ quiescence is regulated by an array of factors. In some instances, they do not activate and hair loss occurs.

Study Details

The researchers determined the metabolism of hair follicle stem cells is unique from other skin cells. Cellular metabolism occurs when nutrients necessary for cell division break down, create energy and react to their environment. The metabolism process makes use of enzymes that changenutrients to generate metabolites. Hair follicle stem cells gradually consume a form of sugar, known as glucose, from the body’s bloodstream. The glucose is processed to gradually create a metabolite known as pyruvate. The cells subsequently send pyruvate to the mitochondria (the portion of the cell that generates energy) or convert pyruvate to another metabolite referred to as lactate.

The researchers blocked the generation of lactate in mice. This prevented the activation of hair follicle stem cells. The UCLA team worked with University of Utah Rutter lab academicians to boost lactate production in mice. This hastened the activation of hair follicle stem cells, causing an increase in the hair cycle. Prior to this, no one knew boosting or decreasing lactate would make an impact on hair follicle stem cells. Now that the researchers have determined how changing lactate production in mice changes hair growth, they can attempt to identify drugs that can be applied to the skin to produce the same effect.

Drugs of Note

The research groups identified a couple drugs that alter hair follicle stem cells in specific ways to boost lactate production when applied to mice skin. One of the drugs, RCGD423, triggers a cell signaling pathway referred to as JAK-Stat that transmits information from outside cells to the cell nucleus. Research shows JAK-Statactivation causes an increase in the generation of lactate. This spurs the activation of hair follicle stem cells and results in faster hair growth.

The second drug of note, UK5099, stops pyruvate from entering mitochondria. This forces the generation of lactate within the hair follicle stem cells, boosting the rate at which hair grows in mice. These experimental drugs were strictly used during pre-clinical testing. They have not been tested in human beings. Nor have these drugs been approved by the Food and Drug Administration as safe or effective for humans.

Why the Study Matters

This study is important as it provides plenty of insight into the many ways in which stem cells are activated. The idea of using drugs to catalyze hair growth by way of hair follicle stem cells is quite promising considering the millions of individuals who are bald or going bald. The researchers’ findings will help improve the understanding of how metabolism affects hair growth as well as stem cells.

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Stem cell agency eyes survival options – Capitol Weekly

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News

by DAVID JENSEN posted 08.14.2017

Californias $3 billion stem cell research agency, which is facing its financial demise in a few short years, has formed a team of its directors to tackle transition planning and examine possible alternatives, including ones that would extend its life.

The first meeting of the group of directors is tentatively scheduled for Sept. 18.Jonathan Thomas, chairman of the governing board of theCalifornia Institute for Regenerative Medicine(CIRM), as the agency is formally known, said earlier this summer:

The legislature has asked that we put together and start thinking about a transition plan, which can contemplate a variety of factors.In response to a question last week, a spokesman for the agency,Kevin McCormack, said that a notice with more details would be posted 10 days prior to the meeting.

At a meeting in June, Thomas laid out the need for the transition team. He said all options are on the table including asking the legislature for cash or to place a measure on the ballot for more bond funding.

The agencys only real source of money is state bonds, authorized by voters in 2004. It has roughly $600 million left. The agency has projected it will run out of cash for new awards in mid 2020, althoughthat could vary, depending on whether it slows down the pace of awards.

Several directors at the board meeting in June expressed a sense of urgency about dealing with the fate of the agency. CIRM DirectorJeff Sheehy, a member of the San Francisco board of supervisors and an HIV/AIDS patient advocate, voiced concern about the uncertain nature of the agencys future.

Sheehy said,It seems to me that we will be talking about a substantial scaling back of the organization in2020.Weve kind of created this expectation that we were going to go to 2018 and come back with new money.

Sheehy referred to talk that a new bond initiative might be launched in 2018, a move that the boards former chairman,Robert Klein, has publicly advanced. Sheehy said, however, that he spoke with Klein, who told him that he wasnow considering 2020 instead.Kleins method would require the gathering of hundreds of thousands of valid voter signatures to place the proposal on the ballot and would bypass the legislature.

The year 2020 includes a presidential election, which has higher voter turnout and generally is considered a better time to win approval of bond measures. Presumably, the agency might be able to secure extra funding to span any financial gap or, alternatively, lower the frequency of awards to stretch out the cash.

The members of the transition group are Thomas, Sheehy,Art Torres, Steve Juelsgaard, Joe Panetta, Kristiina Vuori, Linda Malkas, Diane Winokur, Shlomo Melmed, Al RowlettandJudy Gasson.Short bios on each of them can be found via this page.

TheCalifornia Stem Cell Reportwill carry an item with the date and location of the September meeting when it becomes available.Eds Note:DavidJensenis a retired newsman who has followed the affairs of the $3 billion California stem cell agency since 2005 via his blog, the California Stem Cell Report,where this story first appeared.He has published more than 4,000 items on California stem cell matters in the past 11 years.

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Outrage over S.Korean stem cell scandal official’s new post – Phys.Org

Posted: August 9, 2017 at 3:44 pm

Hundreds of South Korean scientists expressed outrage Wednesday after a controversial figure accused of covering up a notorious stem cell research fraud was appointed as the country’s top technology official.

Park Ki-Young was appointed to head a newly-created science centre, putting her in charge of allocating government subsidies and budgets for research projects.

But a decade ago Park was a key figure in a scandal involving the fabrication of research by prominent stem cell scientist Hwang Woo-Suk.

“Her name is far from innovation. The name is rather a nightmare to science and technology workers,” a group of 240 young scientists said in a statement.

It called on President Moon Jae-In to scrap the appointment, announced earlier this week, accusing Park of remaining “unrepentant” despite being “at the centre” of the scandal surrounding Hwang.

The scientist was lauded as the “pride of Korea” after claiming to have derived stem cell lines from cloned human embryosa world firstin two articles published in the journal Science in 2004 and 2005.

But his research was later found to be fraudulent and riddled with ethical lapses.

Park played a key role in supporting Hwang and his research projects with generous government subsidies when she served as a presidential aide for science and technology from 2004 to 2006.

She was also one of 15 co-authors of one of Hwang’s Science papers.

She resigned after being accused of covering up crucial flaws in Hwang’s stem cell study and sweeping under the carpet ethical lapses involved in Hwang’s projects that used many human eggs.

Even so she went on to become a biology professor at Sunchon National University.

A labour union of government researchers issued a separate statement calling Park’s new nomination a “death knell” for South Korean science and technology.

The Biology Research Information Centre, a renowned online community of researchers which revealed Hwang’s frauds, also joined the criticism, together with multiple activist groups and the country’s three opposition parties, which asserted she was parachuted into the post because of her connections with Moon.

Explore further: Hwang scandal hurt Korean scientists

Journal reference: Science

2017 AFP

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University of Minnesota bioethicist takes on clinics touting stem-cell studies – Minneapolis Star Tribune

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The clinics offer futuristic-sounding treatments for everything from eye problems to osteoarthritis.

Listed on a government website, they present the opportunity to participate in clinical trials to test the potential of one of the most promising tools in medicine the bodys own stem cells. Its an attractive pitch for many patients, even though some of the clinics charge $6,000 and up to participate.

Now, with a national debate raging over the future of one of the hottest frontiers in 21st-century medicine, a University of Minnesota bioethicist has taken center stage in questioning whether many of these services are legitimate.

You have these businesses that dont have meaningful clinical research going on, the Us Leigh Turner said in an interview. There is a risk for fraud, in that people may be charged thousands of dollars to get an intervention that has no chance of working.

Turner has emerged as a major critic of the clinics, some of which he says have flawed procedures that allow bias to distort the results of treatment studies. He also says allowing clinics to list studies can imply government approval, lending false legitimacy to marketing pitches.

My concern is that you basically take clinicaltrials.gov and transform it into a marketing platform, Turner said.

In the past, Turner has moved beyond academic criticism, reporting several clinics he considered questionable to regulators at the U.S. Food and Drug Administration.

One of them, Celltex Therapeutics Corp., received a warning letter from the FDA for its practices in 2012. The company eventually moved its stem-cell infusion operations to Mexico, but it pushed back against Turner in a complaint lodged with U President Eric Kaler.

Clinics have also fired back at Turners latest critical article, which appeared last month in the medical journal Regenerative Medicine.

Research scientist Duncan Ross of Florida-based Kimera Labs, which was identified in Turners July 19 article as advertising an undisclosed pay-for-participation stem-cell study on clinicaltrials.gov, has threatened legal action.

I encourage you to amend your publication or I am going to bring suit against the institution for defamation or slander, Ross wrote to Turner. I am going to lobby the journal for the retraction of this publication. I followed the letter of the FDA as it exists at this time and I am not going to have my name disparaged because of your lack of interest in due diligence.

Turner said no litigation has materialized, and an editor at Regenerative Medicine said no request for a retraction has been made.

Beverly Hills cosmetic surgeon Dr. Mark Berman who is co-medical director of the national Cell Surgical Network, another clinic group named in Turners article said academic researchers like Turner are misguided and out of touch with real-world medical needs.

We are not taking public funding and using it to our benefit while pursuing scientific excellence were actually trying to help our patients while learning about the treatments and the disease they have, Berman said in an e-mail to the Star Tribune. Frankly, I think this is much more ethical than a major university with billions of endowment dollars taking millions of dollars of taxpayer money so they can build new offices and laboratories to further the study of stem cells.

Stem cells are the undifferentiated raw cells in the body that have the ability to quickly produce copies of themselves and also change into other kinds of cells like bone, muscle and blood cells.

Hospitals have safely used stem-cell transplant procedures to treat cancers for decades, but the FDA has approved just one commercial stem-cell product to date, which is made from infant cord blood and can only be used to produce more blood cells.

One of the most common sources of stem cells in pay-to-participate studies is body fat, often obtained via liposuction and known as adipose-derived stem cells. The fact that a byproduct of liposuction can be turned into a potentially therapeutic substance helps explain why smaller clinics are often affiliated with or run by plastic surgeons and cosmetic surgery centers.

Some critics have called for more oversight by the FDA. FDA officials, for their part, have said they share the excitement over the theoretical promise of stem cells to treat or cure disease by converting into cell types needed by the patient. But the agency has sounded a cautionary tone over the profusion of stem-cell clinics and studies popping up around the country.

Studies so far have not reliably demonstrated the effectiveness of stem-cell treatments, even in some of the most systematically studied conditions, FDA officials wrote in the New England Journal of Medicine in March. This lack of evidence is worrisome.

Turner said that many of the studies advertised on clinicaltrials.gov dont seem geared to produce high-quality data that will be medically useful, especially when they involve open-label study designs, where doctors and patients know what treatments are given, and patients are paying out of their own pockets.

In most clinical trials, study subjects are not charged fees to participate. In contrast, individuals enrolled in what are often called pay-to-participate studies are charged thousands or tens of thousands of dollars, Turners report says. Pay-to-participate studies also risk amplifying placebo effects as a result of the sizable fees companies often charge research participants and the hyperbole used to promote such studies.

Allowing participants to know what treatments are given departs from a typical randomized, blind study in which the intervention is kept secret for a period of time. That practice reduces the risk of a placebo effect, which can run high in medical studies.

A 2010 analysis of studies of irritable bowel syndrome treatments found that nearly 40 percent of 8,400 patients experienced an improvement in their symptoms even though they didnt receive the drug being studied.

Tennessee resident Doug Oliver, a nationally known advocate for stem-cell research who says he was legally blind before his eyes were treated with stem cells, agreed that placebo-controlled trials are the best way to ensure that patients are really being helped by a treatment.

But he argues that the coming age of cellular medicine will also require a wider understanding of how medical evidence is generated.

Oliver said most stem-cell clinics are trying to do the right thing, and many people feel that it wasnt even possible to get true FDA oversight of a stem-cell clinical trial before the signing of the 21st Century Cures Act last December. But even Oliver acknowledges that some clinics have exploited clinicaltrials.gov and disregarded any form of regulation thus far.

You have a group of clinics, which I think is a minority, maybe 20 percent, who are ill-intended, unqualified, or there is a personal and cultural aversion to doing anything that even smacks of following a regulation, he said. There are a number of clinics out there like that, and they are hurting people and they should be shut down.

Joe Carlson 612-673-4779

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Microcephaly brain size linked to mutation in stem cell micro environment – Medical Xpress

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Dr Leonie Quinn looking at Drosophila (vinegar flies) through the microscope. Credit: Stuart Hay, ANU

New research highlights the significant role the surrounding environment of stem cells, known as the niche, might play in the brain size of babies with microcephaly.

Mutations in certain genes have been linked with small brains (microcephaly), dwarfism and other developmental defects. Since the discovery of these microcephaly genes, extensive research has been conducted to determine how they cause smaller brains in patients.

Although much research has focused on defective neural stem cell function as the likely culprit in causing small brains in patients with a mutation in the microcephaly protein WDR62, researchers at the Australian National University (ANU) have found that reduced brain size is caused by loss of WDR62 function in the stem cell microenvironment.

“Using genetic models we found when this gene was mutated in the neural stem cells the brain size wasn’t affected at all. The neural stem cells were reduced but the other cells in the brain compensate,” said Dr Quinn group leader at The John Curtin School of Medical Research at ANU.

“Instead, only reduction of WDR62 in the stem cell microenvironment (or niche) severely reduces brain growth by indirectly causing neural stem cell loss and impaired brain development.”

The work has been done as a collaboration between ANU and Dr Dominic Ng’s team at the University of Queensland.

Dr Quinn said the findings would help researchers not only understand how microcephaly mutations cause small brains in microcephaly patients, but also revealed the important connections between stem cells and their niche required for healthy brain development.

“We knew that the loss of the WDR62 microcephaly gene caused patients to have very small brains, dwarfism and other developmental defects, but we didn’t know the mechanism,” she said.

“By understanding the pathways that cause microcephaly, we will also gather information on how zika virus impacts brain development to cause microcephaly in the babies in Brazil.”

The research has been published in the journal Stem Cell Reports.

Explore further: New insights into how the Zika virus causes microcephaly

More information: Nicholas R. Lim et al. Glial-Specific Functions of Microcephaly Protein WDR62 and Interaction with the Mitotic Kinase AURKA Are Essential for Drosophila Brain Growth, Stem Cell Reports (2017). DOI: 10.1016/j.stemcr.2017.05.015

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Amniotic sac in a dish: Stem cells form structures that may aid of infertility research – Phys.Org

Posted: August 8, 2017 at 1:43 pm

The PASE, or post-implantation amniotic sac embryoid, is a structure grown from human pluripotent stem cells that mimics many of the properties of the amniotic sac that forms soon after an embryo implants in the uterus wall. The structures could be used to study infertility. Credit: University of Michigan

The first few weeks after sperm meets egg still hold many mysteries. Among them: what causes the process to fail, leading to many cases of infertility.

Despite the importance of this critical stage, scientists haven’t had a good way to explore what can go wrong, or even what must go right, after the newly formed ball of cells implants in the wall of the human uterus.

But a new achievement using human stem cells may help change that. Tiny lab-grown structures could give researchers a chance to see what they couldn’t before, while avoiding ethical issues associated with studying actual embryos.

A team from the University of Michigan reports in Nature Communications that they have coaxed pluripotent human stem cells to grow on a specially engineered surface into structures that resemble an early aspect of human development called the amniotic sac.

The cells spontaneously developed some of the same structural and molecular features seen in a natural amniotic sac, which is an asymmetric, hollow ball-like structure containing cells that will give rise to a part of the placenta as well as the embryo itself. But the structures grown at U-M lack other key components of the early embryo, so they can’t develop into a fetus.

It’s the first time a team has grown such a structure starting with stem cells, rather than coaxing a donated embryo to grow, as a few other teams have done.

“As many as half of all pregnancies end in the first two weeks after fertilization, often before the woman is even aware she is pregnant. For some couples, there is a chronic inability to get past these critical early developmental steps, but we have not previously had a model that would allow us to explore the reasons why,” says co-senior author Deborah Gumucio, Ph.D. “We hope this work will make it possible for many scientists to dig deeper into the pathways involved in normal and abnormal development, so we can understand some of the most fascinating biology on earth.” Gumucio is the Engel Collegiate Professor of Cell & Developmental Biology at Michigan Medicine, U-M’s academic medical center.

A steady PASE

The researchers have dubbed the new structure a post-implantation amniotic sac embryoid, or PASE. They describe how a PASE develops as a hollow spherical structure with two distinct halves that remain stable even as cells divide.

One half is made of cells that will become amniotic ectoderm, the other half consists of pluripotent epiblast cells that in nature make up the embryonic disc. The hollow center resembles the amniotic cavity – which in normal development eventually gives rise to the fluid-filled sac that protects and cushions the fetus during development.

Gumucio likens a PASE to a mismatched plastic Easter egg or a blue-and-red Pokmon ball – with two clearly divided halves of two kinds of cells that maintain a stable form around a hollow center.

The team also reports details about the genes that became activated during the development of a PASE, and the signals that the cells in a PASE send to one another and to neighboring tissues. They show that a stable two-halved PASE structure relies on a signaling pathway called BMP-SMAD that’s known to be critical to embryo development.

Gumucio notes that the PASE structures even exhibit the earliest signs of initiating a “primitive streak”, although it did not fully develop. In a human embryo, the streak would start a process called gastrulation. That’s the division of new cells into three cell layersendoderm, mesoderm and ectodermthat are essential to give rise to all organs and tissues in the body.

Collaboration provides the spark

The new study follows directly from previous collaborative work between Gumucio’s lab and that of the other senior author, U-M mechanical engineering associate professor Jianping Fu, Ph.D.

In the previous work, reported in Nature Materials, the team succeeded in getting balls of stem cells to implant in a special surface engineered in Fu’s lab to resemble a simplified uterine wall. They showed that once the cells attached themselves to this substrate, they began to differentiate into hollow cysts composed entirely of amnion – a tough extraembryonic tissue that holds the amniotic fluid.

But further analysis of these cysts by co-first authors of the new paper Yue Shao, Ph.D., a graduate student in Fu’s lab, and Ken Taniguchi, a postdoctoral fellow in Gumucio’s lab, revealed that a small subset of these cysts were stably asymmetric and looked exactly like early human or monkey amniotic sacs.

The team found that such structures could also grow from induced pluripotent stem cells (iPSCs)cells derived from human skin and grown in the lab under conditions that give them the ability to become any type of cell, similar to how embryonic stem cells behave. This opens the door for future work using skin cells donated by couples experiencing chronic infertility, which could be grown into iPSCs and tested for their ability to form proper amniotic sacs using the methods devised by the team.

Important notes and next steps

Besides working with genetic and infertility specialists to delve deeper into PASE biology as it relates to human infertility, the team is hoping to explore additional characteristics of amnion tissue.

For example, early rupture of the amnion tissue can endanger a fetus or be the cause of a miscarriage. The team also intends to study which aspects of human amnion formation also occur in development of mouse amnion. The mouse embryo model is very attractive as an in vivo model for investigating human genetic diseases.

The team’s work is overseen by a panel that monitors all work done with pluripotent stem cells at U-M, and the studies are performed in accordance with laws regarding human stem cell research. The team ends experiments before the balls of cells effectively reach 14 developmental days, the cutoff used as an international limit on embryo researcheven though the work involves tissue that cannot form an embryo. Some of the stem cell lines were derived at U-M’s privately funded MStem Cell Laboratory for human embryonic stem cells, and the U-M Pluripotent Stem Cell Core.

Explore further: Team uses stem cells to study earliest stages of amniotic sac formation

More information: Yue Shao et al, A pluripotent stem cell-based model for post-implantation human amniotic sac development, Nature Communications (2017). DOI: 10.1038/s41467-017-00236-w

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Amniotic sac in a dish: Stem cells form structures that may aid of infertility research – Phys.Org

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Odessa physician offering stem cell therapy – Odessa American

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An Odessa physician who specializes in pain management has begun offering stem cell therapy for inflammation from a variety of arthritis.

Dr. Mandeep Othee of ProCare Interventional Pain Medicine, said stem cell therapy has been around since as early as 1938. It has recently been used to stem inflammation, wound care and post-surgical use to help in healing.

The purpose for me is going to be for inflammation for knee arthritis, shoulder arthritis any sort of arthritic process in the neck, the back; any part of the body, Othee said.

Othee said hes always interested in cutting-edge treatments. As associate medical director of In-Patient Rehabilitation at Medical Center Hospital, Othee oversees care for patients with a variety of orthopedic needs, ranging from stroke patients to those recovering from joint replacement surgery, the hospital website said.

He also specializes in diagnosing and treating neck and low-back pain.

The source of the amniotic stem cells is healthy women who have had C-sections who donate their amniotic fluid to a tissue bank. Othee said it is fully regulated by the U.S. Food and Drug Administration and the cells are purified and frozen to preserve them.

The cells provide cushioning, support and lubrication to a developing fetus in the womb.

Its a similar process in the body, so for example, if we take that same stem cell and inject it into the patients knee, or shoulder, or back, or neck it provides the same cushioning, support, lubrication and inflammation reduction that it does in the developing fetus, Othee said.

He added that there are 226 growth factors in the fluid itself, which includes proteins, lipids electrolytes and the magic element of hyaluronic acid.

Thats the typical injection a patient receives in an orthopedic surgeons office. It basically heals the area, provides collagen synthesis and helps with the re-growth of that lost cartilage , Othee said.

Cartilage wears down over time in the joints and injecting the stem cells greatly increases the patients own healing response. Othee said it works 100,000 times better than Platelet Rich Plasma, which is taking a patients own platelets, spinning it down, putting it into a concentrated format and injecting into the patients knee, shoulder, neck or back, Othee said.

Typically, Othee said hes read studies have shown 30, 90 and 100-day responses that are better than steroid shots or hyaluronic acid injections.

It can help patients avoid or delay joint replacement surgeries.

The product he chose is OrthoFlo made by MiMedx.

I chose them because theyre the biggest and the best, Othee said. Their company specializes in different products. One is OrthoFlo. It contains pro-growth factors (and) no tissue fragments or dead cells. It is highly purified human amniotic fluid.

He noted that thousands of injections have been administered over the last five to 15 years and no reactions, side effects or infections have been reported that hes read about.

Currently, no insurance companies pay for the stem cell therapy, but athletes have been getting these for years in other countries, such as Germany and England, and larger cities such as Houston and Dallas. The cost is $2,200 per injection from Othee.

The patient may be sore for a day or two after the stem cell injection and they are able to walk out of the office without a problem. For any sort of knee injections, Othee said a patient may want to wait a week to start running or doing other activities.

Othee said he usually asks patients to stop taking anti-inflammatory medicine for at least seven days before and after the treatment.

He added that there is no age limit on people who could receive stem cell therapy.

Othee said patients may have tried steroid shots, hyaluronic acid, or platelet rich plasma before stem cell therapy. However, they could skip right to stem cell therapy, he added.

Othee said he has spoken to other doctors with patients who have gone straight to stem cell therapy and it works.

Orthopedic surgeon Dr. Vijay Borra doesnt do stem cell injections. He said he thinks research into stem cells just as an injection for osteoarthritis is still in its infancy.

I think a lot of research now is going into using stem cells to generate chondrocytes, which are cartilage to see if we can plug in focal cartilage deficits. Thats where all the research is now. As far as just injecting stem cells into the joint, were still at the very early stages and theres still very little data as to whether it actually works or not, Borra said.

Borra added that there is a lot of good data using that to generate cartilage.

Theres some data there can be used to plug defects. Its an option for people who have done everything like a steroid or hyaluronic gel injections. Theyve done all that and they dont want a knee replacement, or they have too many medical issues and theyre not a candidate. Then it is an option. If theres nothing else, then stem cell is an option, Borra said.

He added that stem cell therapy is not covered by most insurance plans and the out-of-pocket pay is very high.

Its really like an end-stage resort for someone who doesnt want surgery. Theres really no down side. Its not going to do any damage, so you can always try to see if it helps, Borra said.

When patients come to see him, Borra said he first gives them an x-ray to see what the problem is. Most of the time, its osteoarthritis.

By the time they come to Borra, he said the patient has tried anti-inflammatories, weight loss and therapy.

Theyve already done all that, so I start off with a steroid injection. If it works five, six months some people choose to do two or three a year. If it doesnt work, the next option is gel injections, hyaluronic acid, which is like artificial joint fluid, Borra said.

He said Othee also offers nerve blocks.

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