Tag Archives: skin cells

Skin cells as stem cells – medicine’s next big thing

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Gladstone scientist converts human skin cells into functional brain cells

July 28, 2011 – A scientist at the Gladstone Institutes has discovered a novel way to convert human skin cells into brain cells, advancing medicine and human health by offering new hope for regenerative medicine and personalized drug discovery and development.

In a paper being published online today in the scientific journal Cell Stem Cell, Sheng Ding, PhD, reveals efficient and robust methods for transforming adult skin cells into neurons that are capable of transmitting brain signals, marking one of the first documented experiments for transforming an adult human’s skin cells into functioning brain cells.

“This work could have important ramifications for patients and families who suffer at the hands of neurodegenerative diseases such Alzheimer’s, Parkinson’s and Huntington’s disease,” said Lennart Mucke, MD, who directs neurological research at Gladstone. “Dr. Ding’s latest research offers new hope for the process of developing medications for these diseases, as well as for the possibility of cell-replacement therapy to reduce the trauma of millions of people affected by these devastating and irreversible conditions.”

The work was done in collaboration with Stuart Lipton, M.D., Ph.D., who directs the Del E. Webb Neuroscience, Aging and Stem Cell Research Center at Sanford-Burnham Medical Research Institute. Dr. Ding, one of the world’s leading chemical biologists in stem-cell science, earlier this year joined Gladstone and the faculty at the University of California San Francisco (UCSF), as a professor of pharmaceutical chemistry. Gladstone, which is affiliated with UCSF, is a leading and independent biomedical-research organization that is using stem-cell research to advance its work in its three major areas of focus: cardiovascular disease, neurodegenerative disease and viral infections.

Dr. Ding’s work builds on the cell-reprogramming work of another Gladstone scientist, Senior Investigator Shinya Yamanaka, MD, PhD. Dr. Yamanaka’s 2006 discovery of a way to turn adult skin cells into cells that act like embryonic stem cells has radically advanced the fields of cell biology and stem-cell research.

Embryonic stem cells—”pluripotent” cells that can develop into any type of cell in the human body—hold tremendous promise for regenerative medicine, in which damaged organs and tissues can be replaced or repaired. Many in the science community consider the use of stem cells to be key to the future treatment and eradication of a number of diseases, including heart disease and diabetes. But the use of embryonic stem cells is controversial—which is one reason why Dr. Yamanaka’s discovery of an alternate way to obtain human stem cells, without the use of embryos, is so important.

Dr. Ding’s work extends Dr. Yamanaka’s by offering still another method for avoiding the use of embryonic stem cells and creating an entirely new platform for fundamental studies of human disease. Rather than using models made in yeast, flies or mice for disease research, all cell-reprogramming technology allows human brain, heart and other cells to be created from the skin cells of patients with a specific disease. The new cells created from the skin cells contain a complete set of the genes that resulted in that disease—representing the potential of a far-superior human model for studying illnesses, drugs and other treatments. In the future, such reprogrammed skin cells could be used to test both drug safety and efficacy for an individual patient with, for example, Alzheimer’s disease.

“This technology should allow us to very rapidly model neurodegenerative diseases in a dish by making nerve cells from individual patients in just a matter of days—rather than the months required previously,” said Dr. Lipton.

In the experiments being reported today, Dr. Ding used two genes and a microRNA to convert a skin sample from a 55-year-old woman directly into brain cells. (MicroRNAs are tiny strands of genetic material that regulate almost every process in every cell of the body.) The cells created by Dr. Ding’s experiments exchanged the electrical impulses necessary for brain cells to communicate things such as thoughts and emotions. Using microRNA to reprogram cells is a safer and more efficient way than using the more common gene-modification approach. In ensuing experiments, Dr. Ding hopes to rely only on microRNAs and pharmaceutical compounds to convert skin cells to brain cells, which should lead to more efficient generation of cells for testing and regenerative purposes.

“This will help us avoid any genome modifications,” said Dr. Ding. “These cells are not ready yet for transplantation. But this work removes some of the major technical hurdles to using reprogrammed cells to create transplant-ready cells for a host of diseases.”

Dr. Ding is a senior investigator at the Gladstone Institute of Cardiovascular Disease and a UCSF professor of pharmaceutical chemistry. Dr. Ding, who performed the work described in this paper at The Scripps Research Institute, has pioneered the development and application of innovative chemical approaches to stem-cell biology and regeneration.

About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and biomedical innovation to prevent illness and cure patients suffering from cardiovascular disease, neurodegenerative disease, or viral infections. Gladstone is affiliated with the University of California, San Francisco.

Stem Cell Research Breakthrough

A new technique makes the practice of turning adult skin cells into stem cells much faster and more efficient.

A ‘huge leap forward’ for stem cell research

From usatoday.com

Scientists at the Stanford University School of Medicine may have taken the controversy out of the entire field of stem cell research.

In a paper published online today in the journal Nature, they report that they were able to transform mouse skin cells directly into functioning nerve cells without needing to go through a stem cell stage first.

As they say in their paper, this “could have important implications for studies of neural development, neurological disease modeling and regenerative medicine.”

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A Stem-Cell Discovery Could Help Diabetics

By Alice Park, Time.com

Researchers are inching ever closer to bringing the latest stem-cell technologies from bench to bedside — and are, in the process, learning more about some diseases that long have remained medical black boxes.

This week, scientists at the Harvard Stem Cell Institute (HSCI) reported the first success in generating new populations of insulin-producing cells using skin cells of Type 1 diabetes patients. The achievement involved the newer embryo-free technique for generating stem cells, and marked the first step toward building a treatment that could one day replace a patient’s faulty insulin-making cells with healthy, functioning ones.

The experiment, published in the Proceedings of the National Academy of Sciences, also provided the first good model — in a petri dish — of how Type 1 diabetes develops, giving scientists a peek at what goes wrong in patients affected by the disease. Such knowledge could lead to not only new stem-cell-based treatments, but also novel drug therapies that might improve the symptoms of the disease.

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Mice created from skin cells

From Cox Newspapers

WEST PALM BEACH, Fla. — Scientists at The Scripps Research Institute in San Diego have created healthy adult mice out of mouse skin cells — no sperm, no egg. Just skin.

The feat, described in the scientific journal Nature this week, was intended to prove that adult cells can be reprogrammed backward in their development, until they have all the desirable characteristics of embryonic stem cells.

According to Gerard McGill, a medical ethicist at Duquesne University’s Center for Healthcare Ethics, this means the ability to treat diabetes, Alzheimer’s, Parkinson’s, hearing loss, or spinal cord damage with a patient’s own cells is within reach.

“It proves that reprogrammed cells are equivalent to embryonic stem cells,” McGill said. “Treatments are at least 15 or 20 years away, but they are reasonable.”

Reprogramming mouse skin cells to grow into complete mice required advances in mouse genetics, genetic engineering, stem cell biology and reproductive technology.

The scientists started using standard fetal mouse skin cells. They then genetically engineered viruses to carry genes for four key proteins believed to be able to reprogram a cell’s behavior. The viruses infected the skin cells, forcing them to produce the compounds.

The scientists hand-selected cells that had the most obvious stem-cell-like traits.

The cells were eventually transferred into fertile female mice.

Two of the embryos survived to become fertile adults.

Researchers May Have Found Equivalent of Embryonic Stem Cells

By Rob Stein, WashingtonPost.com

Chinese scientists have bred mice from cells that might offer an alternative to human embryonic stem cells, producing the most definitive evidence yet that the technique could help sidestep many of the explosive ethical issues engulfing the controversial field but raising alarm that the advance could lead to human cloning and designer babies.

In papers published online Thursday by two scientific journals, separate teams of researchers from Beijing and Shanghai reported that they had for the first time created virtual genetic duplicates of mice using skin cells from adult animals that had been coaxed into the equivalent of embryonic stem cells.

The findings were welcomed by supporters and opponents of human embryonic stem cell research as a long-sought vital step in proving that the cells could be as useful as embryonic cells for studying and curing many illnesses.

The results come just as the Obama administration has eased federal restrictions on government funding for embryonic stem cell research, and they could influence how to prioritize millions of dollars in new spending in the field.

But because of concerns that the techniques might make cloning and genetic engineering of embryos easier, the work could reignite calls for a ban on attempts to clone people and for restrictions on genetic manipulation of embryos.

“The implications of this are both enormously important and troublesome,” said Robert Lanza, a stem cell researcher at Advanced Cell Technology in Worcester, Mass. “It revives many of the issues raised by reproductive cloning.”

Many scientists believe human embryonic stem cell research could revolutionize medicine by enabling doctors to use genetically matched tissue to treat many diseases. But the field has been mired in controversy because embryos are destroyed to obtain the cells.

In 2006, scientists discovered that they could induce adult cells to regress to a stage that appeared identical to embryonic stem cells, called induced pluripotent stem (iPS) cells. Although scientists have become increasingly adept at creating and manipulating such cells, questions have lingered about whether they are truly equivalent. The new experiments were designed to put the cells to what has long been considered the most rigorous test.

In the studies, published in the journals Nature and Cell Stem Cell, the researchers used viruses to flip genetic switches in the DNA of skin cells from adult mice to turn them into iPS cells in the laboratory. The researchers then injected some of the iPS cells into very early embryos that are capable of forming a placenta but not of fully developing on their own. The resulting embryos were then transferred into the wombs of surrogate mice.

One team of scientists led by Qi Zhou of the Chinese Academy of Sciences created 37 iPS cell lines, three of which produced 27 live offspring, the first of which they named Tiny. One of the offspring, a 7-week-old male, went on to impregnate a female and produce young of its own. Altogether, the researchers bred at least 100 first-generation mice and hundreds of second-generation mice that were nearly identical genetically to the mice from which the iPS cells were derived.

“This gives us hope for future therapeutic interventions using patients’ own reprogrammed cells,” Fanyi Zeng of Shanghai Jiao Tong University, who worked with Zhou, said during a telephone briefing for reporters.

The second group of researchers, led by Shaorong Gao of the National Institute of Biological Sciences in Beijing, created five iPS cell lines, one of which was able to produce embryos that survived until birth. Although four animals were born, only one lived to adulthood. Nevertheless, the work is “proof that iPS cells are functionally equivalent to embryonic stem cells,” Gao said in a telephone interview.

Other researchers agreed, praising the work as a long-awaited confirmation of the cells’ equivalence.

“This clearly says for the first time that iPS cells pass the most stringent test,” said Konrad Hochedlinger, a stem cell researcher at Harvard University.

Opponents of human embryonic stem cell research said the findings provide the latest in a growing body of evidence for why such research is no longer necessary.

“Nobody has been able to find anything that embryonic stem cells can do that these cells can’t do,” said Richard M. Doerflinger of the U.S. Conference of Catholic Bishops. “This was the last remaining barrier.”

The Chinese scientists and others, however, said continued research on embryonic stem cells remains crucial to validate iPS cells and because it remains unclear which cells will turn out to be most useful for different purposes.

But the cells’ ability to produce almost genetically identical offspring raised the fear that rogue scientists might misuse the technique to attempt to clone humans.

“The culture wars are not over,” said Jonathan D. Moreno, a University of Pennsylvania bioethicist. “There was a lot of celebration about the end of the ethical issues with induced pluripotent stem cells. But this is the paradigm case that shows that the old debates are rapidly being transformed into something even more complicated.”

Lanza also raised the prospect that the techniques could one day be used essentially to steal someone’s DNA to make a baby. “With just a little piece of your skin, or some blood from the hospital, anyone could have your child — even an ex-girlfriend or neighbor,” he wrote in an e-mail. “This isn’t rocket science — with a little practice, any IVF clinic in the world could probably figure out how to get it to work.”

In addition, researchers could genetically engineer traits into the cells before using them to create embryos for designer babies.

“For instance, the technology already exists to genetically increase the muscle mass in animals by knocking out a gene known as mystatin, and could be used by a couple who wants a great child athlete,” Lanza wrote.

Others dismissed such concerns, saying many scientific, ethical and regulatory hurdles remain. They said that just because the process works in mice does not necessarily mean it would work in humans, that many states outlaw human cloning and that federal regulators could step in to prevent it.