Tag Archives: embryonic

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.

Is Stem Cell Research Making Progress?

Three distinguished researchers join NPR host Ira Flatow to discuss the latest adult and embryonic stem cell research news, and explain how the research may be used in humans.

Listen to the Story at NPR

Stem Cells Implantation- A Miracle Cure for Blindness

By Snigdha Taduri for BiomedME.com

In a revolutionary experiment, British scientists have discovered a innovative treatment for curing the most common cause for blindness by using a line of patients own embryonic stem cells. Age related macular degeneration is the most common case of blindness in elderly, with at least 300,000 patients being affected every year- a number that is expected to treble in the next 25 years.

The London Project to Cure Blindness is the world’s first blindness therapy that involves replacing damaged retinal cells with stem cells which entailed injecting cells into the back of the eye to replaced damaged photoreceptors – tiny light-sensitive cells found in the retina and key to vision. The key step in the experiment was the selection of slightly more mature stem cells that turned into photoreceptors and formed connections with the nerves leading to the brain.

Most of the transplanted photoreceptors were rod cells that are responsible for vision in the night. It is believed that transplant of cone cells would help enhance viewing of colour and viewing detail. This transplant combination of rod and cone cells would provide an overall enhanced vision to patients.

This premise of this experiment is based on the belief that human retina houses cells that can be used for such transplants. This pioneering stem cell surgery, spearheaded by researchers at the world-famous Moorfields Eye Hospital in London plans to begin clinical trials on humans in two years.

Lyndon da Cruz, a surgeon at Moorfields says the surgery has the potential to become as commonplace as a cataract surgery in a few years time. Tom Bremridge, chief executive of the Macular Disease Society, said: “This is a huge step forward for patients. We are extremely pleased that the big guns have become involved, because, once this treatment is validated, it will be made available to a huge volume of patients.”

Pfizer, the world’s largest pharmaceutical research company, has announced its financial backing to bring the therapy to patients. Pfizer’s role would be crucial in bringing production of the membranes to an industrial level. Professor Coffey, the project leader for the London Project to Cure Blindness commented: “We have not only the benefit of Pfizer’s experience of the regulatory process and their expertise in stem cell technology but the ability, if this works, to produce on a much larger scale.  It has huge implications, not only for our project, but for the field of regenerative medicine as a whole.  And it is great that Britain is at the forefront of this research.”

New human embryonic stem cell lines eligible for federal research dollars for the first time since 2001

By Karen Kaplan,  LATimes.com

The number of human embryonic stem cell lines eligible to be used in government-funded research just went up by 13.

The National Institutes of Health announced today that 11 new cell lines from Dr. George Daley at Children’s Hospital Boston and two lines from Ali Brivanlou at Rockefeller University in New York became the first additions to the NIH Human Embryonic Stem Cell Registry since President Obama reversed his predecessor’s policy. Under President Bush, only human embryonic stem cells prior to August 2001 were eligible for federal funding.

The new lines were derived from embryos created for fertility treatments and donated by couples who went through a rigorous informed consent process.

And more may be on the way. The NIH said that 96 more lines have been submitted by researchers, including 20 that will be vetted by an advisory committee on Friday.

The additions come nearly nine months after Obama signed an executive order that directed the NIH to make federal research funds available to newer lines of human embryonic stem cells. Scientists were overjoyed and said the decision would accelerate the pace of research into such ailments as diabetes, Alzheimer’s and spinal cord injuries. Details of the policy are available here.

First Reconstitution of an Epidermis from Human Embryonic Stem Cells

From ScienceDaily.com

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Creation Of Multiple Types Of White Blood Cells Directly From Embryonic And Adult Stem Cells

From MedicalNewsToday.com

In an advance that could help transform embryonic stem cells into a multipurpose medical tool, scientists at the University of Wisconsin-Madison have transformed these versatile cells into progenitors of white blood cells and into six types of mature white blood and immune cells.

While clinical use is some years away, the new technique could produce cells with enormous potential for studying the development and treatment of disease. The technique works equally well with stem cells grown from an embryo and with adult pluripotent stem cells, which are derived from adult cells that have been converted until they resemble embryonic stem cells.

If the adult cells came from people with certain bone marrow diseases, the new technique could produce blood cells with specific defects. It could also be used to grow specific varieties of immune cells that could target specific infections or tumors.

The likely most immediate benefit is cells that can be used for safety screening of new drugs, says study leader Igor Slukvin, an assistant professor in the university’s Department of Pathology and Laboratory Medicine.

“Toxicity to the blood-forming system is a key limit on drug development, so these cells could be used for safety testing in any drug development,” says Slukvin, who performs research at the National Primate Research Center in Madison.

Bone marrow stem cells are already used to screen drugs, but the new technique promises to produce large quantities of cells in a dish that can be more exactly tailored to the task at hand, without requiring a constant supply of bone marrow cells from donors.

The development of stem cells into mature, specialized cells is governed by trace amounts of biological signaling molecules, so Slukvin and colleagues Kyung-Dal Choi and Maxim Vodyanik exposed two types of highly versatile stem cells to various compounds.

Eventually they found a recipe that would cause the cells to move through a process of progressive specialization into a variety of adult cells. Slukvin’s study was published in the Journal of Clinical Investigation.

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U.S. Stem Cell Research Seems to Focus on Two Lines

From Drugs.com

Only two of 21 approved human embryonic stem cell lines are routinely used by researchers in the United States, says a new study.

The study found that two cell lines, known as H1 and H9, accounted for 941 of 1,217 requests, or 77 percent, placed by scientists since 1999 for human embryonic stem cell lines housed at the two largest stem cell banks in the country.

Another line, H7, was requested 111 times, and 13 other lines were requested fewer than 10 times.

The study’s authors also found that H9 was discussed in 83 percent of 534 published studies from 1999 to 2008, H1 was discussed in 61 percent and H7 in 24 percent. The total is more than 100 percent because many studies used more than one cell line.

“I was surprised by the results,” Christopher Scott, director of Stanford University’s Program on Stem Cells in Society, said in a news release. “I never imagined that we would find that three-fourths of the requests would be for the same two cell lines.”

The study appears in the Aug. 7 issue of Nature Biotechnology.

Scott and his fellow researchers said the findings raise concerns about the reauthorization process of stem cell lines under way at the U.S. National Institutes of Health. If the lines that have been in use are excluded from federal funding because of ethical considerations, they said, scientists might abandon research on them in favor of other cell lines.

However, they added, the two most-used lines might have abnormalities or other characteristics that would make them less useful than newer lines.

Future NIH policies should preserve scientists’ ability to continue work on the well-studied lines while also encouraging the study of ne

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.

Scientists Reprogram Clearly Defined Adult Cells Into Pluripotent Stem Cells — Directly And Without Viruses

From ScienceDaily.com

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Feds ease restrictions on use of stem cells

By Shankar Vedantam, Washington Post

From SFGate.com

Hundreds of embryonic stem cell lines, whose use in the United States had been curtailed by the Bush administration, can be used to study disorders and develop cures if researchers can show the cells were derived using ethical procedures, according to new rules issued by the federal government Monday.

President Obama had promised during last year’s campaign to ease restrictions on the use of stem cells in research, and has cited the promise of stem cells in finding cures for disorders that have so far proved intractable.

The use of embryonic stem cells was not prohibited under the Bush administration, but federal funds were limited to a very small number of stem cell lines, which choked off most research. The new guidelines, issued by the National Institutes of Health, permit federal funding for research using many of the approximately 700 embryonic stem cell lines that are believed to be in existence.

In a move that drew praise from advocates of stem cell research and bitter criticism from opponents, the NIH said it will allow the use of any existing stem cell line that followed broad ethical principles. Acting NIH Director Raynard Kington said an NIH committee including scientists, ethicists and advocates will evaluate older stem cell lines to assess how each was derived.

He said all embryonic stem cell lines that qualified for federal funding would have to meet a series of ethical requirements: The embryo that was destroyed to create a stem cell line must have been discarded by couples following an in vitro fertilization procedure, and the donors must have been informed that the embryo would be destroyed for stem cell research and made fully cognizant of their choices, including donating the embryo to another couple who want a baby. No donors could have been paid for an embryo, and no threats or inducements could have been used to nudge couples toward donating an embryo.

Kington said the NIH would set up a Web site that would list all the approved stem cell lines.

Almost all of the stem cell lines developed in California are expected to meet the NIH ethics guidelines, said Geoffrey Lomax, senior officer for medical and ethical standards with the California Institute for Regenerative Medicine. The institute was created by a voter initiative in 2004 to support stem cell research.

Lomax said the registry should be a boon to researchers in California by making it easier to use stem cell lines from other states. Previously, scientists would have spent valuable time and money determining whether an out-of-state line met California ethical criteria before they could begin their research. With a national database, they can skip that first step, Lomax said.

“This (registry) will speed things up a bit,” Lomax said. “It creates a level of standardization that is extraordinarily helpful and it removes a lot of uncertainty.”

The use of stem cells in research has become the subject of bitter national controversy, with advocates suggesting it is immoral for the federal government not to fund research that could save thousands of lives, and with opponents arguing it is immoral to fund research that involves destroying embryos.

Chronicle staff writer Erin Allday contributed to this report.