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CSCR Reading List: A Look at the Grant Appeal Process at the California Stem Cell Agency

Posted: August 19, 2012 at 3:53 pm


Here is a list of articles from the California Stem Cell Report as well as CIRM documents dealing with the grant appeal process at the California stem cell agency. The list was prepared on Aug. 16, 2012. To read the entire articles, click on the links.

Articles from the California Stem Cell Report

Aug. 7, 2012
A tiny opening exists for scientists
who failed to win approval last month of their bids for $20 million
research awards from the California stem cell agency.
July 26, 2012
Directors of the California stem cell
agency today approved $151 million in research awards aimed at
commercializing stem cell research and pushing therapies into
clinical treatment....Five of the applications involving appeals were
sent back by the board for more review. (See herehere and here.)
They will be considered again in early September or October.
July 24, 2012
The California stem cell agency's
latest grant round – which is budgeted for $243 million – has
drawn an extraordinary and record outpouring of appeals from more
than half of the scientists rejected by the grant reviewers. Nine of
the 15 applicants who were turned down have filed appeals to the
governing board for its meeting
Thursday
 in Burlingame. No other CIRM grant round
has drawn as high a percentage of appeals, formally known as
extraordinary petitions. (See here
for a story on the previous record 
for percentage of
appeals.)
Aug. 10, 2010

Emotionalism and Potential Favoritism Cited as Need for Changes in CIRM Grant Appeals
Passion and favoritism, democracy and gamesmanship – all are part of the ongoing discussion among directors of the $3 billion California stem cell agency as they try to fix what some of them call a “broken” grant appeal process.

July 19, 2010
UC Davis Scientist Praises CIRM Appeals Change
A stem cell researcher at UC Davis today said a change in the CIRM grant appeals procedure makes “a lot of sense.” Writing on his blog in regard to "extraordinary petitions," Paul Knoepfler said, “I think the proposed change makes a lot of sense and would greatly improve the process. Sometimes the reasons in the petitions are clearly not meritorious and as it now stands, they end up wasting CIRM's time. The last time CIRM received 9 petitions as well, which represented a remarkably large fraction of the total applications. A stricter process would discourage the submission of large numbers of petitions, an important issue given that the number of petitions received by CIRM continues to grow.”

CIRM Finally Discloses Grant Appeal Proposals
The California stem cell agency early today belatedly posted a two-page memo on proposed changes in how it will deal with appeals by scientists whose grant applications have been rejected by reviewers.

July 18, 2010
Sticky, Troubling Appeals by Rejected Researchers Targeted by Stem Cell Agency
A key step in the process for awarding billions of dollars in research grants is “broken,” according to many directors of the California stem cell agency, and major changes are looming that will affect hundreds of scientists.

June 22, 2010
Immunology Grants: CIRM Gives $25 Million to 19 Researchers
Directors of the California stem cell agency today approved $25 million for immunology research, overturning four negative decisions by its grant reviewers. Directors faced a record nine public petitions to reverse its reviewers. After some grumbling, the directors, who see only a summary of the application and reviewer comments, okayed the four.

June 19, 2010
More Grant Appeals Filed: Yamanaka Invoked
The California stem cell agency has set another benchmark, although this is one that it may not want to trot out at international stem cell gatherings. Eight scientists whose applications were rejected for funding by the CIRM grants working group and scientific reviewers are seeking to overturn those decisions at the agency's board meeting in San Diego on Tuesday. It is the largest number of “extraordinary petitions” ever filed and amounts to more than one out of every four applications that were turned down. The total number of applications received was 44. Fifteen were approved. Some of the researchers are likely to appear at the board meeting and make a personal pitch.

May 18, 2010
Competing for California Stem Cell Cash: Rules of the Game Coming Under Scrutiny
Every California stem cell scientist and researcher looking to join the field – be they from academia or business – should pay very close attention to a meeting next week of a key group of directors of the $3 billion California stem cell agency. They plan to discuss possible changes in how scientists compete for stem cell cash, which is no small matter since CIRM has another $2 billion to hand out over the next several years.

CIRM documents

Pre-application review – CIRM report (Jan. 2010) on the process

Extraordinary petition policy – Version as of 5/25/10

Appeal policy – Version as of 5/25/2010

Transcript of July 20, 2010, meeting of CIRM directors Science Subcommittee. Discussion of petitions begins on page 40.

Transcript of the June 22, 2010, CIRM directors meeting. Discussions of extraordinary petitions begin on pages 24 and 67.

Transcript of 5/25/10 Science Subcommittee meeting dealing with appeals issue. Discussion begins on page 99.

Source:
http://californiastemcellreport.blogspot.com/feeds/posts/default?alt=rss

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$70 Million Research Proposal Up Next Week at California Stem Cell Agency

Posted: August 19, 2012 at 3:53 pm


Directors of the $3 billion California
stem cell agency will hold a special, teleconference meeting next
Tuesday to deal with business that was put off last month, including
a new, $70 million research round.
The meeting is necessary because directors could not finish their business July 26 after they lost the supermajority quorum required to do business. They delayed action on a number of
matters, including the translational research proposal, which is
scheduled to be posted as an RFA next month.
The governing board also had discussed
dealing with changes in its intellectual property rules at next week's meeting, but that proposal is not on Tuesday's agenda. The next meeting of the board is Sept. 5 and 6 in San Francisco. The
agency has confirmed that it will be a two-day session.
At least one new appeal is expected to
come up in September in the $243 million disease team round that
consumed so much time in July.
Next week meeting involves a host of
locations throughout California. The public is entitled to
participate in the session from any of those sites. The specific
addresses can be found on the agenda.

Source:
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Stem Cell Therapy for Cerebral Palsy in Panama – Video

Posted: August 18, 2012 at 12:12 pm

17-08-2012 13:38 The biggest thing we've noticed is her ability to track people and her vision. Her cognitive skills have improved. Before her stem cell treatment 7 months ago, she was like a 50 watt light bulb and she is like a 200 watts in comparison. She reacts more, holds her head up more and her hands are nice and open now, not fisted like before. Hand to mouth motion is much easier for her to do. Her range of motion, in general, is much better. She can now raise her hands over her head and she was never able to do that before. Her therapists have seen dramatic changes. Our family has noticed changes. The neurologist has noticed changes. We are very thankful that we were able to get this treatment for her in Panama. We couldn't imagine her not being who she is now. She is 200 times better than what she was.

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Stem Cell Therapy: The Hope and the Hype

Posted: August 18, 2012 at 9:19 am

By Shane Huntington

Pioneering stem cell researcher Prof Martin Pera discusses where stem cell research has been and where its going, the therapeutic potential of stem cell technologies, and what we should and shouldnt expect from this fast-developing research field. With host Dr Shane Huntington.

SHANE HUNTINGTON Over the last couple of decades stem cells have been touted as the key to treating a wide range of diseases, with advantages that exceed surgical repair or even organ transplantation; but work on stem cells, especially those derived from human embryos, has drawn significant public scrutiny. In many countries embryonic stem cell research is tightly regulated, and researchers have been forced to explore other research options. Such restrictions are not present worldwide and, in some countries, regulation has yet to catch up with the science. This can make it especially challenging for patients trying to navigate through the world of therapeutic stem cell technologies, both in trial phase and on the consumer market. To explore these issues and the technology itself we are joined on Up Close by one of the pioneers of stem cell research: Professor Martin Pera, program leader of Stem Cells Australia, and professor of stem cell sciences at the University of Melbourne. Welcome to Up Close, Martin.

MARTIN PERA Thank you.

SHANE HUNTINGTON Could you start by giving us a bit of an overview of what a stem cell is and why these particular cells have generated so much interest over the last two decades?

MARTIN PERA Well, they're really two basic types of stem cells. One type of stem cell we cal pluripotent stem cells. And these can either be derived from very early stage embryos of they can now be created in the lab from adult cells, from patients, through a process we call reprogramming. And pluripotent stem cells are able to give rise to all the tissues of the body. The second class of stem cell is the tissue stem cell, sometimes called adult stem cells. These are stem cells that are minority populations in many adult tissues. They are, essentially, more limited in their potential; they usually only give rise to a few types. Both types of stem cells have two key properties. The first is that they are primitive cells that can give rise to more mature functional cell types like neurons or red blood cells. The second is that they can also divide to produce more stem cells. So stem cells provide a reservoir for tissue regeneration or repair. I think the excitement around pluripotential stem cells in particular has to do with the fact that they can be grown indefinitely in the laboratory and multiplied many times over to make more stem cells and that they can give rise to all the tissues of the body. So for the first time we've got an indefinitely renewable source of any healthy human tissue for use either in the laboratory or in transplantation medicine.

SHANE HUNTINGTON You've been working at the stem cells, essentially, from the beginning, when you and others first discovered that you could, potentially, coax these cells down particular differentiation pathways. Tell us a bit about what that was like back then because I can imagine there would have been an incredible sense of enthusiasm with regards to the possibilities of such cells.

MARTIN PERA Well, we were very excited. Of course, it was known since the 1980s that stem cells could be developed from the mouse embryo. Despite many attempts in the intervening years it proved difficult to derive these cells from other species. Then, in the mid-'90s, Jamie Thomson, in Wisconsin, showed that you could make pluripotent cells from the rhesus monkey embryo. And our laboratory, and a few others, set out to see if we could do this from human embryos. It was incredibly exciting when we first had some success, so that, indeed, we could make these cells and that they could turn in to human tissue-like nerves.

SHANE HUNTINGTON What does it mean in terms of the progress of, essentially, combating a range of diseases at that point in time? It seems as though you had something that looked like it was an answer but, decades later, we're still sort of a fair way off.

MARTIN PERA Well, at those early stages there was incredible promise and incredible potential. One of the most difficult things for us in the field was to convey that promise, and the excitement was not trying to claim that things were going to happen too quickly. To me, it's remarkable that only a little over a decade after human embryonic stem cells were discovered we're already seeing clinical trials of the first human embryonic stem cell derived products for conditions like macular degeneration, a very common cause of blindness. Now, that's remarkable because, as I say, it's only a little over a decade. Even in the drug industry - which is a well travelled paradigm for development of therapeutics - it's not unusual to have 10 to 15 years between the discovery and clinical trials. So I think this is quite remarkable. However, in many areas, we still have a long way to go for many applications.

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Stem Cell Therapy: The Hope and the Hype

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Family ties: Trinity woman with leukemia receives stem cells from brother

Posted: August 17, 2012 at 9:10 pm

CHAPEL HILL Kathy DeClue loves her youngest brother Don Hammed for many reasons. These days, Dons selflessness is at the top of her list.

Don donated the stem cells I received during my transplant, said Kathy, 57, of Trinity, in Randolph County. It was a favor I never thought Id have to ask for. But I would have done the same for him if he needed me to.

Kathy needed the stem cell transplant to treat chronic lymphocytic leukemia (CLL), a cancer of the blood cells. For some CLL patients, the disease progresses slowly and they may never need treatment. For others, like Kathy, the disease was on fast-forward and required aggressive medical attention.

From the start, we knew that the CLL was behaving like a high-risk disease and was resistant to just about all the therapies we have, said James M. Coghill, MD, assistant professor of hematology and oncology at the UNC School of Medicine, a member of UNC Lineberger Comprehensive Cancer Center and the leader of Kathys health care team.

The stem cell transplant on April 25 was the best option for trying to get her disease under control, and Kathy had the luxury of three siblings who were a perfect match to donate stem cells. Shes had a supportive family every step of the way. Im sure they would be willing to donate bone marrow again if she needed it.

Besides Don, 46, of Kernersville, N.C., brother Butch Hammed, 56, and sister Rose Tucker, 60, both of Roanoke, Va., were perfect matches. Having multiple matches is unusual as most patients, at best, have a one-in-four chance of getting a perfect match, Dr. Coghill said.

Don got the nod because he was young, healthy and had never been pregnant, Dr. Coghill said. Generally, we try to go with males as donors because female donors who have been pregnant develop antibodies that can increase the chances of graft vs. host disease or rejection.

Rose, the mother of three children, jumped, cried and screamed when she found out she was a perfect match for her sister and her best friend.

I wanted to be a match and her donor so bad, and I was really disappointed when they went with Don, Rose said. They told me Id have enough to do as her caregiver, and as it turned out, I did.

Rose, who was laid off from her child day care job last year, came to Chapel Hill and tended to Kathys every need during the preparations for the transplant and the 100 days post-transplant that Kathy was required to stay at SECU Family House.

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Protecting prion protein keeps stem cells young

Posted: August 17, 2012 at 9:10 pm

COULD we stem the tide of ageing by delaying the deterioration of stem cells? A new compound that appears to do just that could help us find ways to protect our organs from age-related wear and tear, experiments in mice suggest.

As we age, so do our mesenchymal stem cells (MSCs): their numbers in our bone marrow decline, and those that are left lose the ability to differentiate into the distinct cell types - such as bone, cartilage, fat and possibly muscle cells - that help in the healing process.

"We think this ageing of stem cells may be linked to the onset of some age-related disorders, such as osteoporosis," says Ilaria Bellantuono at the University of Sheffield in the UK.

Earlier research in mice had suggested that the prion protein expressed by MSCs might play a role in holding back stem cell ageing. Mice lacking the prion protein were less able to regenerate blood cells. The study provided more evidence that correctly folded prions serve a useful purpose in the body, despite the role that misfolded prions play in BSE and vCJD.

Bellantuono and her colleagues have now found that the prion protein performs a similar function in humans - older MSCs from human bone marrow expressed less of the protein than younger ones.

In a bid to find a compound that might slow MSC ageing, the team tested numerous molecules known to target prion proteins on dishes of human stem cells. One molecule emerged as a potential candidate - stem cells treated with it produced 300 times the number of cells over 250 days than untreated stem cells. The treated cells kept on dividing for longer.

The team then injected treated cells into the thigh bones of mice, and three days later found that they had produced three times as many new cells as they would normally produce. After five weeks, there were 10 times as many cells.

The new cells appeared to be of higher quality, too, and readily differentiated into bone and fat cells, as well as those that support the tissue and blood vessels.

Bellantuono's team think the molecule works by helping the prions protect the stem cells from the DNA damage associated with normal ageing. When they exposed both treated and untreated cells to hydrogen peroxide - a compound known to cause DNA damage - they found that the treated cells were protected from damage (Stem Cells, DOI: 10.1002/stem.1065).

"You can delay the loss of stem cells' function by manipulating the prion protein," says Bellantuono, who presented the findings at the Aging Online Symposium last month. "In the long term, you may go a long way to maintaining tissue health in [old] age."

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Protecting prion protein keeps stem cells young

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Stem Cells as Blood Vessels=Heart Tx?

Posted: August 17, 2012 at 9:10 pm

Researchers at Kings College London have developed the first artificial functioning blood vessel outside of the body, according to a release from the college. The vessels are made from reprogrammed stem cells from human skin. The team also saw the cells develop into a blood vessel inside the body for the first time.

The hope is that this new technique will eventually lead to a treatment for patients with heart disease. The plan is that the reprogrammed cells would be injected into a leg or even directly into the heart to restore blood flow. Another possibility would be to graft one of the artificially developed vessels into the body as a replacement for blocked or damaged vessels. The research team also believes the newly created vessels could be used to prevent leg amputation in diabetic patients with poor circulation.

The study, which was published in the journal Proceedings of the National Academy of Sciences, reports that the reprogrammed vascular cells have no risk turning into tumors.

The release quotes Professor Qingbo Xu of the British Heart Foundation as saying, "This is very exciting research . . . If we can develop this approach as personalized treatments for patients with the condition, it will be a significant step forward."

The researchers cautioned that this is an early study and that more research needs to be done regarding how this approach will works in patients, but Dr Hlne Wilson, Research Advisor at the British Heart Foundation, said: "The discovery could help lead towards future therapies to repair hearts after they are damaged by a heart attack. As well as playing a part in a possible future regenerative treatment, these cells might also be used in drug screening to find new treatments to tackle inherited diseases."

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New research uses stem cells as possible treatment for arthritis

Posted: August 17, 2012 at 9:10 pm

CTVNews.ca Staff Published Friday, Aug. 17, 2012 8:36AM EDT

A Toronto research team hopes to make hip and knee replacements a thing of the past as it explores the growth of new human cartilage using stem cells.

With an estimated four million Canadians suffering from arthritis, and that number expected to grow to seven million by 2031, doctors are hoping to use the stem cells to treat the deterioration of cartilage in joints. Although hip and knee replacements are a great operation, they improve patients lives in terms of pain, quality and function, theyre not your own joint, Dr. Nizar Mahomed told CTVs Canada AM on Friday. They dont last forever and they bring risks and limitations.

Mahomed, an orthopedic surgeon at Torontos Western Hospital, said 45,000 hip and knee replacement surgeries are performed in Canada each year. Many of the surgeries are to treat the damage left by arthritis, which he said is caused by aging, obesity and injuries.

The incident of arthritis increases with age, so as our population ages the prevalence of arthritis is going to continue to increase.

Mahomed and his colleagues are one of the first research teams in the world that have been able to grow human cartilage.

The team is now embarking on the next stage of the study, which will see the new tissue used in animals.

If we actually make it work in animals then one day well be able to bring it back into patients, said Mahomed.

He added that stem cells hold much hope for medicine in the future as studies are looking at using the cells to regenerate cardiac tissue and in the treatment of nerve and spinal cord injuries.

Mahomed said he hopes within five to 10 years the new technology can be used in human patients while putting an end to joint replacement surgeries.

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New research uses stem cells as possible treatment for arthritis

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Embryonic Stem Cells Survive Freezing

Posted: August 17, 2012 at 9:10 pm

Even after 18 years of frozen storage, human embryos can still produce viable stem cells for drug screening and biomedical research.

By Hayley Dunning | August 16, 2012

Cryopreservation of embryos in fertility centers is common, and concerns over damage to the embryo during thawing were largely allayed by the birth of a healthy boy in 2010 from 20-year old cryopreserved embryo. Last week (August 10), researchers in Thailand reported in BioResearch Open Access that they successfully induced the growth of stem cells from a set of 17- and 18-year-old frozen embryos.

The embryos were thawed, then cultured to the blastocyst stage and co-cultured with human foreskin fibroblasts which acted as feeder cells to maintain the growth of embryonic stem cells. The team used the same method to induce stem cells to grow from fresh embryos for comparison, and in cells from both sources they found similar levels of pluripotency.

The importance of this study is that it identifies an alternative source for generating new embryonic stem lines, using embryos that have been in long-term storage, BioResearch Open Access Editor-in-Chief Jane Taylor told Asian News International.

By Cristina Luiggi

A postdoctoral research fellow at Emory University falsifies stem cell research data.

By Megan Scudellari

Human embryonic stem cells swiftly kill themselves in response to DNA damage.

By Edyta Zielinska

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Embryonic Stem Cells Survive Freezing

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Protecting prion protein keeps stem cells young

Posted: August 17, 2012 at 6:11 pm

COULD we stem the tide of ageing by delaying the deterioration of stem cells? A new compound that appears to do just that could help us find ways to protect our organs from age-related wear and tear, experiments in mice suggest.

As we age, so do our mesenchymal stem cells (MSCs): their numbers in our bone marrow decline, and those that are left lose the ability to differentiate into the distinct cell types - such as bone, cartilage, fat and possibly muscle cells - that help in the healing process.

"We think this ageing of stem cells may be linked to the onset of some age-related disorders, such as osteoporosis," says Ilaria Bellantuono at the University of Sheffield in the UK.

Earlier research in mice had suggested that the prion protein expressed by MSCs might play a role in holding back stem cell ageing. Mice lacking the prion protein were less able to regenerate blood cells. The study provided more evidence that correctly folded prions serve a useful purpose in the body, despite the role that misfolded prions play in BSE and vCJD.

Bellantuono and her colleagues have now found that the prion protein performs a similar function in humans - older MSCs from human bone marrow expressed less of the protein than younger ones.

In a bid to find a compound that might slow MSC ageing, the team tested numerous molecules known to target prion proteins on dishes of human stem cells. One molecule emerged as a potential candidate - stem cells treated with it produced 300 times the number of cells over 250 days than untreated stem cells. The treated cells kept on dividing for longer.

The team then injected treated cells into the thigh bones of mice, and three days later found that they had produced three times as many new cells as they would normally produce. After five weeks, there were 10 times as many cells.

The new cells appeared to be of higher quality, too, and readily differentiated into bone and fat cells, as well as those that support the tissue and blood vessels.

Bellantuono's team think the molecule works by helping the prions protect the stem cells from the DNA damage associated with normal ageing. When they exposed both treated and untreated cells to hydrogen peroxide - a compound known to cause DNA damage - they found that the treated cells were protected from damage (Stem Cells, DOI: 10.1002/stem.1065).

"You can delay the loss of stem cells' function by manipulating the prion protein," says Bellantuono, who presented the findings at the Aging Online Symposium last month. "In the long term, you may go a long way to maintaining tissue health in [old] age."

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Protecting prion protein keeps stem cells young

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