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Category Archives: Stem Cells

Tighter Controls on Stem Cell Grant Budgets Hits Quorum Bump

Posted: October 14, 2012 at 4:00 pm


SAN FRANCISCO – A move to tighten
budget controls on grants from the $3 billion California stem cell
agency stalled Monday, but it appears that the plan is headed for
ultimate approval.

The proposal was up for consideration
by the agency's directors' Science Subcommittee, which could not act
on it after it lost its quorum.
Members of the panel generally favored
the stronger budget controls, but had questions about the specifics
of implementing the plan during closed-door reviews of grant
applications. The proposal is likely to be altered to respond to
those concerns. It would then either come back to the Science
Subcommittee or go to the full board.
The plan would make it clear to
recipients of large grants that approval of an application by the
agency's governing board does not provide a carte blanche to
researchers. Ellen Feigal, senior vice president for research and
development, said it can be “extremely difficult” for CIRM staff
to deal with budget problems in grants following board approval.
The committee also approved a plan to
speed the application process on its next disease team round, which
is aimed at driving research into the clinic. The concept proposal
for that round is scheduled to come before directors later this
month. The round will be limited to “more mature stage” research
that is close to a clinical trial, if not in one. Feigal said 10 to
15 applications are expected.
Another proposal to add more millions
to CIRM's strategic partnership program was also approved.

Source:
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Yamanaka: 'Rejected, Slow and Clumsy'

Posted: October 14, 2012 at 4:00 pm


This week's announcement of the Nobel
Prize
for Shinya Yamanaka brought along some interesting
tidbits, including who was “snubbed” as well as recollections
from the recipient.

Jon Bardin of the Los Angeles Times
wrote the “snubbed” piece and quoted Christopher Scott of
Stanford and Paul Knoepfler of UC Davis about the selection issues.
Bardin's piece mentioned Jamie Thomson and Ian Wilmut as scientists
who also could have been considered for the award but were not named.
Ultimately, Bardin wrote that the award committee was looking for a
“singular, paradigm shifting discovery,” which he concluded was
not the case with Thomson or Wilmut.
How Yamanaka arrived at his research
was another topic in the news coverage, much of it dry as dust.
However, Lisa Krieger of the San Jose Mercury News began her story
with Yamanaka's travails some 20 years ago. At the time, no one was returning his phone
calls as he looked for work, and he was rejected by
50 apparently not-so-farsighted American labs.
But that job search in 1993 came only after Yamanaka
decided he was less than successful as an orthopedic surgeon,
according to an account in JapanRealTime. “Slow and clumsy” was
how Yamanaka described himself.
And so he moved on to research. But
again he reported stumbling. In this case, he found a way to reduce
“bad cholesterol” but with a tiny complication – liver cancer.
That in turn sent him on a journey to learn how cells proliferate and
develop, which led him to the work that won the Nobel Prize.
Yamanaka said his original interest in
orthopedic medicine was stimulated by his father along with the treatments
for injuries young Yamanaka received while playing rugby and learning judo. The JapanRealTime account continued,

“'My father probably still thinks in
heaven that I’m a doctor,' he said in the interview(with Asahi
Shimbun
last April). 'IPS cells are still at a research phase and
have not treated a single patient. I hope to link it to actual
treatment soon so I will be not embarrassed when I meet my father
someday.'”

And then there was, of course, the much-repeated story from the researcher who shared the Nobel with Yamanaka, John Gurdon. He has preserved to this day a
report from a high school biology teacher that said the 15-year-old
Gurdon's desire to become a scientist was “quite ridiculous.”
The teacher, who is unnamed, wrote,

“If he can’t learn simple
biological facts he would have no chance of doing the work of a
specialist, and it would be a sheer waste of time, both on his part
and of those who would have to teach him.”

Source:
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Stem Cell Orthodoxy and Peer Review

Posted: October 14, 2012 at 4:00 pm


Going against the grain can be
difficult as UC Davis stem cell scientist Paul Knoepfler learned
again in connection with his research that dealt with similarities
between cancer and iPS cells.

His “unsettling” findings troubled
some scientists who reviewed his paper prior to its publication in
September in Stem Cells and Development. (See here and here.)
As many readers know, iPS or
reprogrammed adult cells are currently a hot research avenue in stem
cell research because they avoid many of the ticklish ethical and
political problems connected with human embryonic stem cells.
Knoepfler shared his thoughts on the
publication and peer review process on his blog last week. He wrote,

“Not surprisingly...there are certain
members of the stem cell field who would rather focus away from the
ideas that iPS cells are similar in some respects to cancer.”

Knoepfler, whose research was financed
in part by the California stem cell agency, wrote,

“Once we had a manuscript together
comparing iPS cells to cancer cells, we sent it to several high
profile journals without much luck. We thought that the fact that our
data indicated that iPS cells are similar to cancer cells might make
reviewers and editors excited. We thought that the paper was novel
and thought provoking in a number of ways. At the same time I
realized the theme of the paper would be controversial. 

“I would say two general things about
the review process at the two journals that turned down the paper.
First, the reviewers at these journals were enormously helpful with
their suggestions and helped us improve the paper substantially.
Second, they were clearly very uncomfortable with the notion that iPS
cells are related in some ways to cancer so unsettled in fact that I
believe it influenced their reviews.”

At one journal, a reviewer said the
findings were either “not sufficiently novel” or “trivial.”
“Little useful insights” said another. And a third said, “many
unsettling results....”
Knoepfler commented on this blog,

“Yeah, it may be unsettling that iPS
cells share traits with cancer cells, but if that is the reality,
isn’t it important that people know that and think about it, talk
about it, and address the issue with eyes open?”

Knoepfler's item and similar comments
from other researchers that can found elsewhere on the Internet
indirectly raise questions about the California stem cell agency's process
of peer review of applications for hundreds of millions of dollars in
funding, especially in the wake of this summer's unprecedented rash of appeals of decisions by grant reviewers.
The key question is whether the agency's closed-door process reinforces orthodoxy or, in fact, is all but controlled by what
amounts to scientific conventional wisdom. Obviously, no researcher
likes to see a paper rejected or a grant denied. But the record
number of appeals at CIRM and other private complaints could well indicate
that potentially profitable proposals are receiving a less than
welcome reception behind closed doors from agency reviewers.
The agency's board itself is
hard-pressed to make such determinations. It is hamstrung by
procedures that do not permit it to expand an application directly –
only a staff-written summary. Names of applicants and institutions
are censored, although the board is required by law to discuss in
public most aspects of a research proposal. Exceptions are permitted for proprietary information. Additionally, a handful of the 29 members of the governing board do participate in the reviews, which come before final action by the board. 
Currently the agency is pushing hard to
commercialize stem cell research and fulfill at least some of the
promises to voters that were made in 2004. To do that, the agency may
well have to step outside of the normal comfort zone of the good
burghers of stem cell science.

Source:
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Stem cells from muscle tissue ‘may help cure neurodegenerative diseases’

Posted: October 13, 2012 at 2:19 pm

Washington, October 13 (ANI): In a new study, researchers have taken the first steps to create neural-like stem cells from muscle tissue in animals.

"Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can't harvest neural stem cells from the brain or spinal cord without harming the donor," Osvaldo Delbono, lead author of the study from Wake Forest Baptist Medical Center, said.

"Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumours and other diseases, although more studies are needed," Delbono said.

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice.

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumours, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumours were found.

"Right now, patients with glioblastomas or other brain tumours have very poor outcomes and relatively few treatment options," Alexander Birbrair, first author of the study, said.

"Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumours but also for other central nervous system diseases," he added.

The findings of the study have been published online in the journals Experimental Cell Research and Stem Cell Research. ANI)

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Stem cells from muscle tissue 'may help cure neurodegenerative diseases'

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Posted: October 12, 2012 at 11:29 pm

WASHINGTON (BP) -- A Japanese researcher who discovered a way to produce stem cells that act like embryonic ones without their lethal consequences has won a Nobel Prize. "I thought, we can't keep destroying embryos for our research. There must be another way." -- Shinya Yamanaka The Nobel Foundation awarded its 2012 prize in physiology or medicine to Shinya Yamanaka, who was able to reprogram adult skin cells into cells that have virtually the identical properties of embryonic ones, which have the ability to change into any cell or tissue in the body. In the Oct. 8 announcement, Yamanaka, 50, shared the Nobel Prize with British scientist John Gurdon, 79, whose work in 1962 paved the way for the Japanese researcher's breakthrough.

Unlike embryonic stem cells, reprogrammed cells -- also known as induced pluripotent stem (iPS) cells - do not cause harm to a donor. The extraction of embryonic stem cells, however, results in the destruction of a days-old human embryo.

The "life" issue also was a theme in the awarding of this year's Nobel Prize for literature. Chinese writer Mo Yan, a critic of his country's coercive population control policy, received the award Oct. 11 from the Nobel Foundation, which is based in Stockholm, Sweden.

Yan's most recent novel, "Wa," "illuminates the consequences of China's imposition of a single-child policy," according to the Nobel news release.

Yamanaka, the Nobel physiology/medicine winner who teaches at Kyoto University in Japan, was motivated in his search for a safe way to produce embryonic-like cells by a look through a microscope at a human embryo stored at a fertility clinic in the late 1990s.

"When I saw the embryo, I suddenly realized there was such a small difference between it and my daughters," Yamanaka told The New York Times in 2007. "I thought, we can't keep destroying embryos for our research. There must be another way."

In 2006, he found a way to induce adult cells to take on embryonic-like, or "pluripotent," qualities. Embryonic stem cells are considered "pluripotent," meaning they can develop into all of the different cell types in the body. Adult stem cells typically have been regarded as "multipotent," meaning they can form many, though not all, of the body's cell types. Yamanaka's work showed adult cells could become "pluripotent" and thereby avoid the ethical problems with embryonic stem cells.

Pro-life bioethics specialist Wesley Smith lauded the Nobel Foundation's decision to reward Yamanaka, writing on his blog, "This is so deserved!"

"Bravo Dr. Yamanaka! You proved that good ethics leads to splendid science," Smith said.

The ability of stem cells to convert to other cells and tissues has provided great hope for developing cures for various diseases. Embryonic stem cell research has yet to provide any treatments for human beings and has been plagued by tumors in lab animals, however. Reprogrammed, or iPS, cells have demonstrated promising results but have not been used in human trials.

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Stem-cell transplant claims debunked

Posted: October 12, 2012 at 11:29 pm

Hisashi Moriguchi presented his work at the New York Stem Cell Foundation meeting this week.

AP/Press Association

From the beginning, it seemed too good to be true. Days after Kyoto University biologist Shinya Yamanaka won a Nobel prize for his 2006 discovery of induced pluripotent stem (iPS) cells (see 'Cell rewind wins medicine Nobel'), Hisashi Moriguchi a visiting researcher at the University of Tokyo claimed to have modified that technology to treat a person with terminal heart failure. Eight months after surgical treatment in February, said a front-page splash in the Japanese newspaper Yomiuri Shimbun yesterday, the patient was healthy.

But after being alerted to the story by Nature, Harvard Medical School and Massachusetts General Hospital (MGH), where Moriguchi claimed to have done the work, denied that the procedure had taken place. No clinical trials related to Dr Moriguchi's work have been approved by institutional review boards at either Harvard University or MGH, wrote David Cameron, a spokesman for Harvard Medical School in Boston, Massachusetts. The work he is reporting was not done at MGH, says Ryan Donovan, a public-affairs official at MGH, also in Boston.

A video clip posted online by the Nippon News Network and subsequently removed showed Moriguchi presenting his research at the New York Stem Cell Foundation meeting this week.

If true, Moriguchis feat would have catapulted iPS cells into use in a wide range of clinical situations, years ahead of most specialists' predictions. I hope this therapy is realized in Japan as soon as possible, the head of a Tokyo-based organization devoted to helping children with heart problems told Yomiuri Shimbun.

But there were reasons to be suspicious. Moriguchi said he had invented a method to reprogram cells using just two chemicals: microRNA-145 inhibitor and TGF- ligand1. But Hiromitsu Nakauchi, a stem-cell researcher at the University of Tokyo, says that he has never heard of success with that method. He adds that he had also never heard of Moriguchi before this week.

Moriguchi also said that the cells could be differentiated into cardiac cells using a 'supercooling' method that he had invented. Thats another weird thing, says Nakauchi.

The article in which Moriguchi presented his two-chemical method, published in a book1 describing advances in stem-cell research, includes paragraphs copied almost verbatim from other papers. The section headed 2.3 Western blotting, for example, is identical to a passage from a 2007 paper by Yamanaka2. Section 2.1.1, in which Moriguchi describes human liver biopsies, matches the number of patients and timing of specimen extractions described in an earlier article3, although the name of the institution has been changed.

When contacted by Nature, Moriguchi stood by his publication. We are all doing similar things so it makes sense that wed use similar words, he says. He did admit to using other papers as reference.

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Neural-like stem cells from muscle tissue may hold key to cell therapies for neurodegenerative diseases

Posted: October 12, 2012 at 11:29 pm

ScienceDaily (Oct. 12, 2012) Scientists at Wake Forest Baptist Medical Center have taken the first steps to create neural-like stem cells from muscle tissue in animals.

Details of the work are published in two complementary studies published in the September online issues of the journals Experimental Cell Research and Stem Cell Research.

"Reversing brain degeneration and trauma lesions will depend on cell therapy, but we can't harvest neural stem cells from the brain or spinal cord without harming the donor," said Osvaldo Delbono, M.D., Ph.D., professor of internal medicine at Wake Forest Baptist and lead author of the studies.

"Skeletal muscle tissue, which makes up 50 percent of the body, is easily accessible and biopsies of muscle are relatively harmless to the donor, so we think it may be an alternative source of neural-like cells that potentially could be used to treat brain or spinal cord injury, neurodegenerative disorders, brain tumors and other diseases, although more studies are needed."

In an earlier study, the Wake Forest Baptist team isolated neural precursor cells derived from skeletal muscle of adult transgenic mice (PLOS ONE, Feb. 3, 2011).

In the current research, the team isolated neural precursor cells from in vitro adult skeletal muscle of various species including non-human primates and aging mice, and showed that these cells not only survived in the brain, but also migrated to the area of the brain where neural stem cells originate.

Another issue the researchers investigated was whether these neural-like cells would form tumors, a characteristic of many types of stem cells. To test this, the team injected the cells below the skin and in the brains of mice, and after one month, no tumors were found.

"Right now, patients with glioblastomas or other brain tumors have very poor outcomes and relatively few treatment options," said Alexander Birbrair, a doctoral student in Delbono's lab and first author of these studies. "Because our cells survived and migrated in the brain, we may be able to use them as drug-delivery vehicles in the future, not only for brain tumors but also for other central nervous system diseases."

In addition, the Wake Forest Baptist team is now conducting research to determine if these neural-like cells also have the capability to become functioning neurons in the central nervous system.

Co-authors of the studies are Tan Zhang, Ph.D., Zhong-Min Wang, M.S., Maria Laura Messi, M.S., Akiva Mintz, M.D., Ph.D., of Wake Forest Baptist, and Grigori N. Enikolopov, Ph.D., of Cold Spring Harbor Laboratory.

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Neural-like stem cells from muscle tissue may hold key to cell therapies for neurodegenerative diseases

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Could Stem Cells Treat Autism? Newly Approved Study May Tell

Posted: October 12, 2012 at 11:29 pm

FRIDAY, Oct. 12 (HealthDay News) -- Autism researchers have been given the go-ahead by the U.S. Food and Drug Administration to launch a small study in children with autism that evaluates whether a child's own umbilical cord blood may be an effective treatment.

Thirty children with the disorder, aged 2 to 7, will receive injections of their own stem cells from umbilical cord blood banked by their parents after their births. All of the cord blood comes from the Cord Blood Registry, the world's largest stem cell bank.

Scientists at Sutter Neuroscience Institute, in Sacramento, Calif., said the placebo-controlled study will evaluate whether the stem cell therapy helps improve language and behavior in the youngsters.

There is anecdotal evidence that stem cell infusions may have a benefit in other conditions such as cerebral palsy, said lead study investigator Dr. Michael Chez, director of pediatric neurology at the institute.

"We're hoping we'll see in the autism population a group of patients that also responds," Chez said. Other autism and stem cell research is going on abroad, but this study is the first to use a child's own cord blood stem cells.

Chez said the study will involve only patients whose autism is not linked to a genetic syndrome or brain injury, and all of the children will eventually receive the stem cells.

Two infusions will take place during the 13-month study. At the start of the research, the children will be split into two groups, half receiving an infusion of cord blood stem cells and half receiving a placebo. At six months, the groups will swap therapies. The infusions will be conducted on an outpatient basis with close monitoring, Chez said.

"We're working with Sutter Children's Hospital, who does our oncology infusions with the same-age children," he said. "They are very experienced nurses who work with preschool and school-age kids to help them get through medical experiences."

Each child and his or her parents will be given a private room with a television and videos, beverages, and perhaps a visit from the hospital's canine therapy dog, and then a topical anesthetic will be applied to the arm to numb the skin before intravenous needle placement. A hematology expert will be giving the infusions and monitoring for safety, said Chez, who noted that each child will be watched closely for an hour and a half before heading home. They will be seen the next day as well for a safety check.

At six, 12 and 24 weeks, the researchers will measure behavioral and language changes in the children, and other changes noted by parents and the children's doctors will be logged as well.

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Could Stem Cells Treat Autism? Newly Approved Study May Tell

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Early Results Show Promise for Stem Cells in Treating Chronic Liver Failure

Posted: October 11, 2012 at 2:19 pm

Stem cell transfusions may someday replace the need for transplants in patients who suffer from liver failure caused by hepatitis B, according to a new study coming out of Beijing. . The results are published in the October issue of STEM CELLS Translational Medicine. Worldwide more than 500,000 people die each year from this condition.

Durham, NC (PRWEB) October 11, 2012

In China, hepatitis B virus (HBV) infection accounts for the highest proportion of liver failure cases. While liver transplantation is considered the standard treatment, it has several drawbacks including a limited number of donors, long waiting lists, high cost and multiple complications. Our study shows that mesenchymal stem cell (MSCs) transfusions might be a good, safe alternative, said Fu-Sheng Wang, Ph.D., M.D., the studys lead author and director of the Research Center for Biological Therapy (RCBT) in Beijing.

Wang along with RCBT colleague, Drs. Ming Shi and Zheng Zhang of the Research Center for Biological Therapy, The Institute of Translational Hepatology led the group of physician-scientists from the centers and Beijing 302 Hospital who conducted the study.

MSC transfusions had already been shown to improve liver function in patients with end-stage liver diseases. This time, the researchers wanted to gauge the safety and initial efficacy of treating acute-on-chronic liver failure (ACLF) with MSCs. The American Association for the Study of Liver Diseases and the European Association for the Study of the Liver define ACLF as an acute deterioration of pre-existing chronic liver disease usually related to a precipitating event and associated with increased mortality at three months due to multisystem organ failure. The short-term mortality rate for this condition is more than 50 percent.

MSCs have self-renewing abilities and the potential to differentiate into various types of cells. More importantly, they can interact with immune cells and cause the immune system to adjust to the desired level.

Of the 43 patients in this pilot study each of whom had liver failure resulting from chronic HBV infection 24 were treated with MSCs taken from donated umbilical cords and 19 were treated with saline as the control group. All received conventional therapy as well. The liver function, adverse events and survival rates were then evaluated during the 48-week or 72-week follow-up period.

Along with increased survival rates, the patients liver function improved and platelet count increased. No significant side effects were observed throughout the treatment and follow-up period.

While the results are preliminary and this pilot study includes a small number of patients, MSC transfusions appear to be safe and may serve as a novel therapeutic approach for HBV-associated ACLF patients, Dr. Shi said.

The study also highlights several key issues that will need to be considered in the design of future clinical studies, such as the optimal type of stem cells that will be infused, the minimum effective number of the cells and the best route of administration, Dr. Wang added.

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Early Results Show Promise for Stem Cells in Treating Chronic Liver Failure

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10/11/2012 10:05 JAPAN Nobel Prize for Yamanaka, scientific research and ethics must go hand in hand

Posted: October 11, 2012 at 2:19 pm

10/11/2012 10:05 JAPAN Nobel Prize for Yamanaka, scientific research and ethics must go hand in hand by Pino Cazzaniga Research on iPS (induced pluripotent stem cells) can produce stem cells from adult cells, for use in regenerative medicine. Shinya Yamanakas discovery reveals that research on embryonic stem cells is unnecessary, saving the lives of many embryos. The Japanese researcher has searched for new ways driven by ethical question.

Tokyo (AsiaNews) - Shinya Yamanaka, fresh from the Nobel Prize for medicine, states that science and ethics must go hand in hand. Interviewed by the Mainichi Shimbun after the award, he said: "I would like to invite ethical experts as teachers at my laboratory and work to guide iPS [induced pluripotent stem] cell research from that direction as well. The work of a scientific researcher is just one part of the equation. "

Yamanaka, 50, found that adult cells can be transformed into cells in their infancy, stem cells (iPS), which are, so to speak, the raw material for the reconstruction of tissue irreparably damaged by disease. For regenerative medicine the implications of Yamanaka's discovery are obvious. Adult skin cells can for example be reprogrammed and transformed into any other cell that is desired: from the skin to the brain, from the skin to the heart, from the skin to elements that produce insulin.

"Their discovery - says the statement of the jury that awarded him the Nobel Prize on October 8 - has revolutionized our understanding of how cells and organisms develop. Through the programming of human cells, scientists have created new opportunities for the study of diseases and development of methods for the diagnosis and therapy ".

These "opportunities" are not only "scientific", but also "ethical". Much of the scientific research and global investment is in fact launched to design and produce stem cells from embryos, arriving at the point of manipulating and destroying them, facing scientists with enormous ethical problems.

" Ethics are really difficult - Yamanaka explainsto Mainichi - In the United States I began work on mouse experiments, and when I returned to Japan I learned that human embryonic stem cells had been created. I was happy that they would contribute to medical science, but I faced an ethical issue. I started iPS cell research as a way to do good things as a researcher, and I wanted to do what I could to expand the merits of embryonic stem cells. If we make sperm or eggs from iPS cells, however, it leads to the creation of new life, so the work I did on iPS cells led to an ethical problem. If we don't prepare debates for ethical problems in advance, technology will proceed ahead faster than we think.. "

The "ethical question" Yamanaka pushed to find a way to "not keep destroying embryos for our research."

Speaking with his co-workers at the University of Kyoto, immediately after receiving the award, Yamanaka showed dedication and modesty.

"Now - he said - I strongly feel a sense of gratitude and responsibility" gratitude for family and friends who have supported him in a demanding journey of discovery that lasted decades; responsibility for a discovery that gives hope to millions of patients. Now iPS cells can grow into any tissue of the human body allowing regeneration of parts so far irretrievably lost due to illness.

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10/11/2012 10:05 JAPAN Nobel Prize for Yamanaka, scientific research and ethics must go hand in hand

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