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

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

Science is working on it.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

David Scadden

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Visit link:
Researchers study secrets of aging via stem cells - Harvard Gazette

Skin Stem Cells Comments Off on Researchers study secrets of aging via stem cells – Harvard Gazette | April 18th, 2017

Like drag car racers revving their engines at the starting line, stem cells respond more quickly to injury when they've been previously primed with one dose of a single protein, according to a study from the Stanford University School of Medicine.

Mice given the priming protein recover muscle function more quickly after damage, their skin heals more rapidly and even the shaved area around the injury regrows hair more quickly, the study found. Harnessing the power of this protein may one day help people recover more quickly from surgery or restore youthful vigor to aging stem cells.

"We're trying to better understand wound healing in response to trauma and aging," said Thomas Rando, MD, PhD, professor of neurology and neurological sciences. "We've shown that muscle and bone marrow stem cells enter a stage of alertness in response to distant injury that allows them to spring into action more quickly. Now we've pinpointed the protein responsible for priming them to do what they do better and faster."

Rando, who also directs Stanford's Glenn Center for the Biology of Aging, is the senior author of the study, which will be published April 18 in Cell Reports. Former postdoctoral scholar Joseph Rodgers, PhD, is the lead author. Rodgers is now an assistant professor of stem cell biology and regenerative medicine at the University of Southern California.

Potential therapy

"Our research shows that by priming the body before an injury you can speed the process of tissue repair and recovery, similar to how a vaccine prepares the body to a fight infection," Rodgers said. "We believe this could be a therapeutic approach to improve recovery in situations where injuries can be anticipated, such as surgery, combat or sports."

Normally, adult, tissue-specific stem cells are held in a kind of cellular deep freeze called quiescence to avoid unnecessary cell division in the absence of injury. In a 2014 paper published in Nature, Rodgers and Rando showed in laboratory mice that an injury to the muscle of one leg caused a change in the muscle stem cells of the other leg. These cells entered what the researchers called an "alert" phase of the cell cycle that is distinct from either fully resting or fully active stem cells.

The fact that muscle stem cells distant from the injury were alerted indicated that the damaged muscle must release a soluble factor that can travel throughout the body to wake up quiescent stem cells. Rodgers and his colleagues found that a protein called hepatocyte growth factor, which exists in a latent form in the spaces between muscle cells and tissue, can activate a critical signaling pathway in the cells by binding to their surfaces. This pathway stimulates the production of proteins important in alerting the stem cells. But it wasn't known how HGF itself became activated.

In the new study, Rodgers and his colleagues identified the activating factor by injecting uninjured animals with blood serum isolated from animals with an induced muscle injury. (Mice were anesthetized prior to a local injection of muscle-damaging toxin; they were given pain relief and antibiotics during the recovery period.) After 2.5 days, the researchers found that muscle stem cells from the recipient animals were in an alert state and completed their first cell division much more quickly than occurred in animals that had received blood serum from uninjured mice.

"Clearly, blood from the injured animal contains a factor that alerts the stem cells," said Rando. "We wanted to know, what is it in the blood that is doing this?"

Increased levels of a protein

The researchers found that the serum from the injured animals had the same levels of HGF as the control serum. However, it did have increased levels of a protein called HGFA that activates HGF by snipping it into two pieces. Treating the serum with an antibody that blocked the activity of HGFA eliminated the recovery benefit of pretreatment, the researchers found.

In a related experiment, exposing the animals to a single intravenous dose of HGFA alone two days prior to injury helped the mice recover more quickly. They scampered around on their wheels sooner and their skin healed more quickly than mice that received a control injection. They also regrew their hair around the shaved surgical site more completely than did the control animals.

"Just like in the muscles, we saw the responses in the skin were dramatically improved when the stem cells were alerted," Rando said.

In addition to pinpointing possible ways to prepare people for surgeries or other situations in which they might sustain wounds, the researchers are intrigued by the role HGF and HGFA might play in aging. It's known that the pathway activated by these proteins is less active in older people and animals.

"Stem cell activity diminishes with advancing age, and older people heal more slowly and less effectively than younger people. Might it be possible to restore youthful healing by activating this pathway?" said Rando. "We'd love to find out."

The work is an example of Stanford Medicine's focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

Go here to read the rest:
Protein primes mouse stem cells to quickly repair injury, study finds ... - Science Daily

Skin Stem Cells Comments Off on Protein primes mouse stem cells to quickly repair injury, study finds … – Science Daily | April 18th, 2017

BY: DUSTIN BATTY

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

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

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

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

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

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

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

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

Skin Stem Cells Comments Off on Stem cells can now be gathered from urine samples – The Plaid Zebra (blog) | April 17th, 2017

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

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

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

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

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

Use of IPS cells is regarded as morally acceptable by those who oppose use of human embryonic stem cells, because they cant form an entire embryo. This is the reasoning of the Catholic Church. But since the EPS cells can make whole embryos, at least in mice, how the church will react is unclear.

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

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

Better tool

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

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

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

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

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

Organs for transplant

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

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

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

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

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

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

bradley.fikes@sduniontribune.com

(619) 293-1020

See original here:
Stem cell invented that can grow into any tissue in the body - The ... - The San Diego Union-Tribune

Skin Stem Cells Comments Off on Stem cell invented that can grow into any tissue in the body – The … – The San Diego Union-Tribune | April 16th, 2017

Stem cells are a rapidly advancing field of biological research. Since Dr. James Thomson first cultivated human embryonic stem cells at the University of Wisconsin - Madison in the late 1990s, this field of researched has exploded with potential. The links below provide access to a curriculum developed under the supervision of Dr. Thomson as well as the co-directors and staff of the UW Stem Cell & Regenerative Medicine Center. The material has been reviewed for accuracy by the scientists actually conducting the research and was compiled and formatted by Craig Kohn, a high school teacher with research experience, for a high school audience. The PowerPoint presentation works in conjunction with the notesheet, allowing for students to work independently if preferred. More information about specific instructional practices can be found below in Teacher Notes. PowerPoint: http://bit.ly/ted-stemcells Notesheet: http://bit.ly/ted-stemcellsnotesheet Quiz: http://bit.ly/ted-stemcellsquiz Additional resources about stem cells can be found at: http://www.stemcells.wisc.edu/node/386 http://stemcells.nih.gov/Pages/Default.aspxhttp://www.stemcellschool.org/http://www.nursingdegree.net/blog/750/25-best-blogs-for-following-stem-cell-research/

See the original post here:
What are stem cells? - Craig A. Kohn | TED-Ed

Skin Stem Cells Comments Off on What are stem cells? – Craig A. Kohn | TED-Ed | April 16th, 2017

GETTY - STOCK IMAGE

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

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

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

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

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

GETTY - STOCK IMAGE

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

Our cell cultures open new doors to brain research

Professor Jens Schwamborn

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

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

GETTY - STOCK IMAGE

Getty Images

1 of 9

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

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

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

"The cells can transmit and process signals.

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

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

GETTY - STOCK IMAGE

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

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

"The production of tissue cultures is highly elaborate.

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

The study was published in the Stem Cell Reports journal.

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

Skin Stem Cells Comments Off on Scientists one step closer to turning stem cells into BRAIN | Health … – Express.co.uk | April 14th, 2017

It would seem the beautiful foxglove plant has more uses than just the garden.

A novel drug screen in liver-like cells shows that cardiac glycosides, which are found in the leaves of the digitalis or foxglove plant, could reduce low-density lipoprotein (LDL) cholesterol differently than statins, potentially providing a new treatment for patients.

The foxglove plant in bloom on MUSC's campus.

These findings were reported by the Medical University of South Carolina researcher Stephen A. Duncan, D.Phil., SmartState Chair of Regenerative Medicine at MUSC, and colleagues in the April 6 issue of Cell Stem Cell.

Duncan said the glycosides were identified through a stem cell screen for compounds that could be used off-label for the treatment of high cholesterol. The nice thing about finding new uses for drugs already on the market is that they can be used relatively quickly in patients because most of the needed safety trials have already been completed.

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

Duncan and his graduate student Max Cayo, who is finishing his M.D. at the Medical College of Wisconsin, developed a drug screen to identify an alternative to statins. Apolipoprotein B (apoB) is a molecule that liver cells use to make LDL. Drugs that decreased apoB could potentially lower cholesterol independently of the LDL receptor in FH patients and also in patients with other forms of high cholesterol.

FH was a perfect model for testing alternatives to statins. Yet the rarity of FH meant these liver cells were scarce. Duncans group made induced pluripotent stem cells out of skin fibroblasts taken from a single patient with FH. Stem cells continually double their numbers while in culture. This meant that a sample of converted skin cells from a single patient with FH provided a renewable source of liver-like cells that retained the mutation.

The group tested these liver-like cells with the SPECTRUM library, a collection of 2,300 pharmaceuticals, many of which have reached clinical trials. Surprisingly, all nine cardiac glycosides in the collection, some widely prescribed for heart failure, reduced apoB in liver-like cells from the patient with FH. In further tests, they also lowered apoB in human hepatocytes and in mice engineered to grow normal human livers without the FH mutation.

Next, the team combed through more than five thousand medical records of patients prescribed cardiac glycosides for heart failure who also had LDL cholesterol records. Similar drops in LDL levels were observed in these patients as in a matching group of patients prescribed statins.

This study provides the first evidence that cardiac glycosides could potentially reduce LDL cholesterol independently of the LDL receptor, where statins act, by reducing apoB.

The cardiac glycosides are always prescribed with care, as they are known to be toxic at high doses. However, they could offer inexpensive life-saving options for patients with FH. Additionally, a cardiac glycoside in a low dose could conceivably provide an added benefit to patients already taking a statin. Duncan is exploring plans for a clinical trial that would determine the correct dose in hypercholesterolemia patients.

Using patient stem cells to screen drugs that are already on the market is a great way to investigate treatments for liver diseases.

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

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

Read more:
SPECTRUM Drug Screen Reveals Fox Gloves Can Treat High Cholesterol - Technology Networks

Skin Stem Cells Comments Off on SPECTRUM Drug Screen Reveals Fox Gloves Can Treat High Cholesterol – Technology Networks | April 14th, 2017

Science Daily

Brain tissue from a petri dish: Stem cell research -- ScienceDaily Science Daily The most complex organ in humans is the brain. Due to its complexity, it is extremely difficult to do scientific experiments on it -- ones that could help us to ... and more »

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

Skin Stem Cells Comments Off on Brain tissue from a petri dish: Stem cell research — ScienceDaily – Science Daily | April 14th, 2017

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

The perilous wait now begins for Jonathan Pitre.

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

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

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

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

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

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

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

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

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

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

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

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

Skin Stem Cells Comments Off on His stem-cell transplant complete, the wait begins for Jonathan Pitre – Ottawa Citizen | April 14th, 2017

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

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

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

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

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

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

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

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

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

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

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

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

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

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

View original post here:
Spray-On Skin: 'Miracle' Stem Cell Treatment Heals Burns Without ... - Newsweek

Skin Stem Cells Comments Off on Spray-On Skin: ‘Miracle’ Stem Cell Treatment Heals Burns Without … – Newsweek | April 11th, 2017

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

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

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

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

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

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

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

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

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

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

See the original post:
Now You Can Harness Your Own Stem Cells - Coronado Eagle ... - Coronado Eagle and Journal

Skin Stem Cells Comments Off on Now You Can Harness Your Own Stem Cells – Coronado Eagle … – Coronado Eagle and Journal | April 11th, 2017

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

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

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

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

Science

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

Clinical Trials

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

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

istock jm1366

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

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

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

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

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

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

Skin Stem Cells Comments Off on The International Stem Cell Corporation, a Company Dedicated to Curing Parkinson’s Disease – Huffington Post | April 11th, 2017

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Reference:

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

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

Read more from the original source:
Partial De-differentiation Converts Skin Cells into Blood Vessel Cells ... - Technology Networks

Skin Stem Cells Comments Off on Partial De-differentiation Converts Skin Cells into Blood Vessel Cells … – Technology Networks | April 11th, 2017

M

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

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

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

advertisement

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

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

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

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

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

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

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

Muhammad Ali and Parkinsons disease: Was boxing to blame?

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

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

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

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

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

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

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

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

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

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

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

Skin Stem Cells Comments Off on Mighty morphed brain cells cure Parkinson’s in mice, but human trials still far off – STAT | April 10th, 2017

Science Daily

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

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

Skin Stem Cells Comments Off on Stem cell drug screen yields potential alternative to statins – Science Daily | April 10th, 2017

Science Daily

Turning skin cells into blood vessel cells while keeping them young Science Daily Other methods reprogram a cell so that it directly assumes a new identity, bypassing the stem-cell state. In the last few years, scientists have begun to explore another method, a middle way, that can turn back the clock on skin cells so that they lose ...

Go here to read the rest:
Turning skin cells into blood vessel cells while keeping them young - Science Daily

Skin Stem Cells Comments Off on Turning skin cells into blood vessel cells while keeping them young – Science Daily | April 10th, 2017

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Researchers from the University of Illinois at Chicago have identified a molecular switch that converts skin cells into cells that make up blood vessels, which could ultimately be used to repair damaged vessels in patients ...

For decades, American waistlines have been expanding and there is increasing cause for alarm. Researchers from the Charles E. Schmidt College of Medicine at Florida Atlantic University make the case that metabolic syndromea ...

Scientists at the Medical University of South Carolina (MUSC) have found that a class of heart failure drugs might decrease low-density lipoprotein (LDL) cholesterol levels in patients who do not respond to statins. In a ...

In a New England Journal of Medicine (NEJM) editorial published last week, Debabrata Mukherjee, M.D., provides expert commentary on bioresorbable stents, an alternative to the traditional stents used in patients with cardiac ...

Cedars-Sinai Heart Institute investigators have learned how cardiac muscle cells react to a certain type of injury that can be caused by open-heart surgery. The findings point to a new potential way to help these hearts recover ...

Scientists from King's College London have developed a new blood test that is more sensitive in detecting damaged heart muscle caused by a heart attack.

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Read more from the original source:
Turning skin cells into blood vessel cells while keeping them young - Medical Xpress

Skin Stem Cells Comments Off on Turning skin cells into blood vessel cells while keeping them young – Medical Xpress | April 9th, 2017

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

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

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

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

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

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

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

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

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

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

Skin Stem Cells Comments Off on Stem Cell Drug Screen Yields Potential Alternative to Statins – R & D Magazine | April 8th, 2017

No two stem cells are identical, even if they are genetic clones. This stunning diversity is revealed today in an enormous publicly available online catalogue of 3D stem cell images. The visuals were produced using deep learning analyses and cell lines altered with the gene-editing tool CRISPR. And soon the portal will allow researchers to predict variations in cell layouts that may foreshadow cancer and other diseases.

The Allen Cell Explorer, produced by the Allen Institute for Cell Science in Seattle, Washington, includes a growing library of more than 6,000 pictures of induced pluripotent stem cells (iPS) key components of which glow thanks to fluorescent markers that highlight specific genes.

The Cell Explorer complements ongoing projects by several groups that chart the uniqueness of single cells at the level of DNA, RNA and proteins. Rick Horwitz, director of the Allen Institute for Cell Science, says that the institutes images may hasten progress in stem cell research, cancer research and drug development by revealing unexpected aspects of cellular structure. You cant predict the outcome of a football game if you know stats on all the players but have never watched a game.

The project began about a year ago with adult skin cells that had been reprogrammed into an embryonic-like, undifferentiated state. Horwitz and his team then used CRISPRCas9 to insert tags in genes to make structures within the cells glow. The genes included those that code for proteins that highlight actin filaments, which help cells to move and maintain their shape. It quickly became clear that the cells, which were all genetic clones from the same parent cell, varied in the placement, shape and number of their components, such as mitochondria and actin fibres.

Computer scientists analysed thousands of the images using deep learning programs and found relationships between the locations of cellular structures. They then used that information to predict where the structures might be when the program was given just a couple of clues, such as the position of the nucleus. The program learned by comparing its predictions to actual cells.

The deep learning algorithms are similar to those that companies use to predict peoples preferences, Horwitz says. If you buy a chainsaw at Amazon, it might then show you chain oil and plaid shirts.

The 3D interactive tool based on this deep learning capability should go live later this year. At the moment, the site shows a preview of how it will work using side-by-side comparisons of predicted and actual images.

Benjamin Freedman, a cell biologist at the University of Washington in Seattle, looks forward to playing with the Cell Explorers predictive function once the Allen Institute team has taught their algorithm to recognize more iPS cells that have been changed genetically or chemically. For example, Freedman says he could delete a gene related to kidney disease in one of the fluorescently tagged stem cells from the Allen Institute and see how the mutation affects the glowing structure. Then he could use the sites modelling tool to determine how other cellular components might be altered. Ultimately, Freedman says, we want to understand processes at the cellular level that cause disease in the kidney as a whole.

In the coming months, Allen Institute researchers will update the site with images of stem cells at different stages of cell division, and as they transform into distinct cell types, such as heart and kidney cells. Catching cells at different time points can be crucial to identifying fundamental processes, says Horwitz.

Allen Institute for Cell Science

Structural differences in the DNA (purple) and cellular membrane (blue) of genetically identical stem cells.

The Allen Institutes visual emphasis on stem cells dovetails with a number of efforts to catalogue other aspects of cells. For example, the London-based charity Cancer Research UK is creating interactive virtual-reality models of breast cancer cells in tumours. And an international effort called the Human Cell Atlas seeks to define all human cell types in terms of their molecular profiles, including DNA sequences, RNA transcripts and proteins.

Aviv Regev, a computational biologist at the Broad Institute in Cambridge, Massachusetts, who is working on the Human Cell Atlas, says that the Allen Cell Explorer complements her project by focusing on the look of cellular features as opposed to how genes, RNA and proteins interact within the cell. The community is accepting that there are a lot of differences between cells that we thought were the same until recently, she says, so now were taking an unbiased approach to learn about pieces in the puzzle we didnt know existed before.

Originally posted here:
Machine learning predicts the look of stem cells - Nature.com

Skin Stem Cells Comments Off on Machine learning predicts the look of stem cells – Nature.com | April 8th, 2017

Last week, a patient with blurry vision in his right eye walked into a doctors office and became the first person to receive reprogrammed stem cells from a donor to treat his age-related macular degeneration.

The patient a Japanese man in his 60s is not alone, as four other patients have been approved for the procedure by Japan's health ministry. The first medical case was reported on March 28 by Nature.

In a one-hour operation by surgeon Yasuo Kurimoto, the patient received skin cells from a human donor at Kobe City Medical Center General Hospital. The donors skin cells were reverse engineered into induced pluripotent stem (iPS) cells. These cells are often seen as a game-changer in the world of regenerative medicine as they have the ability to become almost any type of cell in the body.

In this case, the iPS cells were turned into retinal cells, which were then implanted into the retina of the patient, who has age-related macular degeneration. It is hoped the procedure will stop the progression of the disease, which can lead to blindness. The transplantis not being touted as a cure for the condition, merely a prevention methodfrom further damage.

During the procedure, the surgical team injected 50 microliters of liquid containing 250,000 retinal cells into the patients eye, according to the Japan Times. The real test, however, will be the next phase of monitoring.

What sets this transplant apart is also what makes the recovery process precarious. Doctors will need to keep a careful watch on the patient, as iPS cells from a donor are not a genetic match and could cause an immune rejection.

At this point, you might remember a similar case in 2014 with a Japanese woman at the same hospital. She also received retinal cells derived from iPS cells, however hers were taken from her own skin, not a donor's.

"A key challenge in this case is to control rejection," said Riken researcher Masayo Takahashi to the Japan Times. "We need to carefully continue treatment."

In an update, the team said the Japanese woman was doing well and her vision had not declined. They decided to change track and use donor cells for this study because it holds a more viable future for such transplants.

It's hoped, if all goes well here, that researchers can create a bank of donor stem cells. Such a future would cut down on costs and reduce wait times, as cultivating ones own cells can take several months. However, there's stillmuch to be done.

After the procedure, Takahashi told a press conference that the surgery went well. They will continue to monitor the situation and provide further updates in the future.

Read more:
Man Receives Reprogrammed" Stem Cells From Donor In Medical First - IFLScience

Skin Stem Cells Comments Off on Man Receives Reprogrammed" Stem Cells From Donor In Medical First – IFLScience | April 4th, 2017