Probing matters of the heart: Stem cell differentiation study sheds light on genetic basis of heart disease

ScienceDaily (Sep. 14, 2012) The fate of an embryonic stem cell, which has the potential to become any type of body cell, is determined by a complex interaction of genes, proteins that bind DNA, and molecules that modify those genes and proteins.

In a new paper, biologists from MIT and the University of California at San Francisco have outlined how those interactions direct the development of stem cells into mature heart cells. The study, the first to follow heart-cell differentiation over time in such detail, could help scientists better understand how particular mutations can lead to congenital heart defects. It could also assist efforts to engineer artificial heart tissue.

"We're hoping that some of the information we've been able to glean from our study will help us to approach a new understanding of heart development, and also lead to the possibility of using cells that are generated in a dish to replace heart cells that are lost as a consequence of aging and disease," says Laurie Boyer, an associate professor of biology at MIT and a senior author of the paper, which appears in the Sept. 13 online edition of Cell.

Research in Boyer's lab focuses on how DNA is organized and controlled in different cell types to create the wide variety of cells that make up the human body.

Inside a cell, DNA is wrapped around proteins called histones, which help control which genes are accessible at any given time. Histones may be tagged with different chemical modifications, which influence whether a particular stretch of DNA is exposed or hidden.

"These modifications cause structural changes that can act as docking sites for other factors to bind," says Joe Wamstad, a postdoc in Boyer's lab and one of the lead authors of the Cell paper. "It may make the DNA more or less accessible to manipulation by other factors, helping to ensure that you don't express a gene at the wrong time."

In this paper, the researchers found that histone-modification patterns shift rapidly as a stem cell differentiates. Furthermore, the patterns reveal genes that are active at different stages, as well as regulatory elements that control those genes.

Tracking development

To discover those patterns, the researchers grew mouse embryonic stem cells in a lab dish and treated them with proteins and growth factors that drive heart cell development. The cells could be followed through four distinct stages, from embryonic stem cells to fully differentiated cardiomyocytes (the cells that compose heart muscle). At each stage, the researchers used high-throughput sequencing technology to analyze histone modifications and determine which genes were being expressed.

"It's basically watching differentiation over time in a dish, and being able to take snapshots of that and put it all together to try to understand how the complex process of cardiac commitment is regulated," Boyer says.

The rest is here:
Probing matters of the heart: Stem cell differentiation study sheds light on genetic basis of heart disease

Professional Conferences Held as Part of Cryo-Save's Cord Blood Awareness Months

Zutphen, The Netherlands (ots/PRNewswire) -

Cryo-Save Group promotes the awareness of cord blood storage and stem cell therapies at several professional conferences held throughout eastern and southern Europe.

It is with great pleasure that Cryo-Save supports the awareness, research and advancement of cord blood storage and therapies by taking part in and sponsoring four major conferences in Cyprus, Bosnia-Herzegovina, Serbia and Hungary during the months of September and October.

Stem cells are becoming ever more important in the medical field as a way to treat a broad variety of malignant and non-malignant diseases such as leukemia's and other childhood cancers. Patients suffering from sickle cell anemia have been considered cured after being treated with stem cells.[1] Over 4,000 clinical trials using cord blood stem cells are taking place to treat diseases such as cerebral palsy, diabetes and autism with many more potential clinical trials continuing to develop.

"Cryo-Save's efforts to inform the medical community about advances in regenerative medicine means that patients suffering from diseases treatable with stem cells can also become better informed," says Dr. Cherie Daly, Medical Affairs Manager Cryo-Save. "Having a series of events and programs as part of Cord Blood Awareness Months makes an even stronger impact on the meaningfulness of this research and its application." Cryo-Save Group will continue its commitment to promoting the storage of cord blood and stem cells even after Cord Blood Awareness Months by offering several customer related promotions.

A half-day conference in Limassol, Cyprus will be held September 15 giving the medical community the opportunity to talk with scientists specialized in stem cells about the latest applications and cord blood and tissue regulatory requirements. Cryo-Save's Medical Affairs Manager Dr. Cherie Daly, member of ITERA (International Tissue Engineering Research Association), member of the Advisory Panel for the Parents' Guide to Cord Blood Foundation and Dr. Sally Sennitt, Cryo-Save Lab Director, will be there to present on these topics.

The third International Conference on Regenerative Medicine: Stem Cells, Genetic Engineering and Biotechnologies will take place September 21 in Banja Luka, Bosnia and Herzegovina. Arnoud van Tulder, Cryo-Save Group CEO, will present on the "Importance of Family Stem Cell Banking: Over 10 Years of Leading Experience." Medical professionals will also present on subjects like applications of cord blood, stem cell therapies and pharmacogenomics.

--------------------------------------------------

1. University of Illinois at Chicago (2012, June 18). Chicago woman cured of sickle cell disease. ScienceDaily. Retrieved September 12, 2012, from http://www.sciencedaily.com/releases/2012/06/120618194714.htm

With the idea of broadening perspectives and expanding knowledge in the areas of regenerative medicine, genetics and clinical applications, Cryo-Save Serbia will be sponsoring the fifth International Symposium on Regenerative and Personalised Medicine on October 4 in Belgrade. Leading speakers such as Prof. Dr. Daniel Surbek from the University of Bern, Switzerland and Maja Stojiljkovic Petrovic, PhD of IMGGE, University of Belgrade will present their research and other works pertaining to stem cell application in tissue engineering at the symposium.

Excerpt from:
Professional Conferences Held as Part of Cryo-Save's Cord Blood Awareness Months

Professional Conferences Held as Part of Cryo-Save’s Cord Blood Awareness Months

Zutphen, The Netherlands (ots/PRNewswire) -

Cryo-Save Group promotes the awareness of cord blood storage and stem cell therapies at several professional conferences held throughout eastern and southern Europe.

It is with great pleasure that Cryo-Save supports the awareness, research and advancement of cord blood storage and therapies by taking part in and sponsoring four major conferences in Cyprus, Bosnia-Herzegovina, Serbia and Hungary during the months of September and October.

Stem cells are becoming ever more important in the medical field as a way to treat a broad variety of malignant and non-malignant diseases such as leukemia's and other childhood cancers. Patients suffering from sickle cell anemia have been considered cured after being treated with stem cells.[1] Over 4,000 clinical trials using cord blood stem cells are taking place to treat diseases such as cerebral palsy, diabetes and autism with many more potential clinical trials continuing to develop.

"Cryo-Save's efforts to inform the medical community about advances in regenerative medicine means that patients suffering from diseases treatable with stem cells can also become better informed," says Dr. Cherie Daly, Medical Affairs Manager Cryo-Save. "Having a series of events and programs as part of Cord Blood Awareness Months makes an even stronger impact on the meaningfulness of this research and its application." Cryo-Save Group will continue its commitment to promoting the storage of cord blood and stem cells even after Cord Blood Awareness Months by offering several customer related promotions.

A half-day conference in Limassol, Cyprus will be held September 15 giving the medical community the opportunity to talk with scientists specialized in stem cells about the latest applications and cord blood and tissue regulatory requirements. Cryo-Save's Medical Affairs Manager Dr. Cherie Daly, member of ITERA (International Tissue Engineering Research Association), member of the Advisory Panel for the Parents' Guide to Cord Blood Foundation and Dr. Sally Sennitt, Cryo-Save Lab Director, will be there to present on these topics.

The third International Conference on Regenerative Medicine: Stem Cells, Genetic Engineering and Biotechnologies will take place September 21 in Banja Luka, Bosnia and Herzegovina. Arnoud van Tulder, Cryo-Save Group CEO, will present on the "Importance of Family Stem Cell Banking: Over 10 Years of Leading Experience." Medical professionals will also present on subjects like applications of cord blood, stem cell therapies and pharmacogenomics.

--------------------------------------------------

1. University of Illinois at Chicago (2012, June 18). Chicago woman cured of sickle cell disease. ScienceDaily. Retrieved September 12, 2012, from http://www.sciencedaily.com/releases/2012/06/120618194714.htm

With the idea of broadening perspectives and expanding knowledge in the areas of regenerative medicine, genetics and clinical applications, Cryo-Save Serbia will be sponsoring the fifth International Symposium on Regenerative and Personalised Medicine on October 4 in Belgrade. Leading speakers such as Prof. Dr. Daniel Surbek from the University of Bern, Switzerland and Maja Stojiljkovic Petrovic, PhD of IMGGE, University of Belgrade will present their research and other works pertaining to stem cell application in tissue engineering at the symposium.

Excerpt from:
Professional Conferences Held as Part of Cryo-Save's Cord Blood Awareness Months

Scientists bring new efficiency to stem cell reprogramming

In this image of mouse embryonic fibroblasts undergoing reprogramming, each colored dot represents messenger RNA associated with a specific gene that is active in cells being reprogrammed. Red dots represent mRNA for the gene Sall4, green is Sox2, and blue is Fbxo15. The researchers determined that Sox2 activates Sall4 and then activates the downstream gene Fbxo15, creating a gene hierarchy in the later phase of reprogramming. Credit: Dina Faddah/Whitehead Institute

Several years ago, biologists discovered that regular body cells can be reprogrammed into pluripotent stem cellscells with the ability to become any other type of cell. Such cells hold great promise for treating many human diseases.

These induced pluripotent stem cells (iPSCs) are usually created by genetically modifying cells to overexpress four genes that make them revert to an immature, embryonic state. However, the procedure works in only a small percentage of cells.

Now, new genetic markers identified by researchers at Whitehead Institute and MIT could help make that process more efficient, allowing scientists to predict which treated cells will successfully become pluripotent.

The new paper, published in the Sept. 13 online edition of Cell, also identifies new combinations of reprogramming factors that produce iPSCs, according to the researchers.

Led by Rudolf Jaenisch, a Whitehead Founding Member and an MIT professor of biology, the study is the first to examine genetic changes that occur in individual cells as they become pluripotent. Previous studies have only looked at gene-expression changes in large populations of cellsnot all of which will actually reprogrammaking it harder to pick out genes involved in the process.

"In previous studies, you weren't able to detect the few cells that expressed predictive pluripotency markers. The really cool part of this study is that you can detect two or three cells that express these important genes early, which has never been done before," says Dina Faddah, a graduate student in Jaenisch's lab and one of the paper's lead authors.

The other lead author is Yosef Buganim, a postdoc at Whitehead Institute.

Single-cell analysis

In 2007, scientists discovered that adult human cells could be reprogrammed by overexpressing four genesOct4, Sox2, c-Myc and Klf4. However, in a population of cells in which those genes are overexpressed, only about 0.1 to 1 percent will become pluripotent.

Continue reading here:
Scientists bring new efficiency to stem cell reprogramming

Tracking stem cell reprogramming: Biologists reveal genes key to development of pluripotency, in single cells

ScienceDaily (Sep. 13, 2012) Several years ago, biologists discovered that regular body cells can be reprogrammed into pluripotent stem cells -- cells with the ability to become any other type of cell. Such cells hold great promise for treating many human diseases.

These induced pluripotent stem cells (iPSCs) are usually created by genetically modifying cells to overexpress four genes that make them revert to an immature, embryonic state. However, the procedure works in only a small percentage of cells.

Now, new genetic markers identified by researchers at MIT and the Whitehead Institute could help make that process more efficient, allowing scientists to predict which treated cells will successfully become pluripotent.

The new paper, published in the Sept. 13 online edition of Cell, also identifies new combinations of reprogramming factors that produce iPSCs, according to the researchers.

Led by Rudolf Jaenisch, an MIT professor of biology and member of the Whitehead Institute, the study is the first to examine genetic changes that occur in individual cells as they become pluripotent. Previous studies have only looked at gene-expression changes in large populations of cells -- not all of which will actually reprogram -- making it harder to pick out genes involved in the process.

"In previous studies, you weren't able to detect the few cells that expressed predictive pluripotency markers. The really cool part of this study is that you can detect two or three cells that express these important genes early, which has never been done before," says Dina Faddah, a graduate student in Jaenisch's lab and one of the paper's lead authors.

The other lead author is Yosef Buganim, a postdoc at the Whitehead Institute.

Single-cell analysis

In 2007, scientists discovered that adult human cells could be reprogrammed by overexpressing four genes -- Oct4, Sox2, c-Myc and Klf4. However, in a population of cells in which those genes are overexpressed, only about 0.1 to 1 percent will become pluripotent.

In the new study, Jaenisch's team reprogrammed mouse embryonic fibroblast cells and then measured their expression of 48 genes known or suspected to be involved in pluripotency at several points during the process. This allowed them to compare gene-expression profiles in cells that became pluripotent, those that did not, and those that were only partially reprogrammed.

Here is the original post:
Tracking stem cell reprogramming: Biologists reveal genes key to development of pluripotency, in single cells

RNL BIO, a South Korean adult stem cell firm, introduces its autologous stem cell therapeutics in Turkey to treat …

SEOUL, South Korea, Sept. 13, 2012 /PRNewswire/ --RNL Bio (www.rnl.co.kr) announced on Sep 11, 2012 that it signed the agreement with RST Biomedikal Sanayi A.S. (RST), a Turkish company, to license RNL Bio's stem cell technology. Turkey is the 6th country where RNL Bio's stem cell technology has entered. This is one of the major accomplishments that RNL BIO has long focused on establishing the so-called 'Stem Cell Silk Road' with South Korean stem cell technology to give hope to patients with intractable diseases in the world.

RST as a licensee will pay the $5 million fee upfront within 60 days from the agreement and will continue to pay the running royalty of 15% of the revenue, which could be up to $ 200 million. RST will benefit from the geographical advantages of Turkey where Western, Arabic and Oriental cultures are crossed. It plans to establish a GMP facility and invite patients from Europe and Middle East early next year.

Ilknur Erdemin, CEO of RST said, "We expect to improve public health and the quality of life in Turkey through stem cell therapy technology imported from RNL BIO in treating various intractable diseases. We will also grow Turkey to one of the world's most renowned country in regards to medical tourism with RNL's stem cell technology in combination with Turkish World's Heritage." To begin with, RST will focus on the treatment ofdiabeticcomplications, autoimmune diseases, cerebral palsy, and degenerative arthritis with RNL's autologous adipose derived stem cell technology. Stem cell therapy has already been allowed by Turkish health authority since 2011. Turkey actively promotes the industry of regenerative medicine and makes a quick move to expand in related fields.

Dr. Jeong-Chan Ra, president of RNL Stem Cell Technology Institute said, "This licensing deal will be a good opportunity todevelopRNL's stem cell technology to be the world's standards and tofulfillmy goal to make RNL BIO a company that will have treated and helped the most patients suffering from intractable diseases." He had a seminar introducing his stem cell studies to Turkish attendees from related fields and distinguished invitees one day prior to signing licensing agreement.

Read the original:
RNL BIO, a South Korean adult stem cell firm, introduces its autologous stem cell therapeutics in Turkey to treat ...

Eastday-Stem cell donors reaches 3,000 mark

The number of hematopoietic stem cell donors in the Chinese mainland hit 3,000 on Friday, as the country saw a rapid increase in donors over the last four years, an official said.

Hong Junling, director of the China Marrow Donor Program, a nonprofit organization under the auspices of the Red Cross Society of China, said that 3,000 people have donated their blood cells to domestic and overseas patients through the program.

"It took 12 years for the CMDP to witness the growth of stem cell donors from the first case to the 1,000th case from 1996 to 2008, yet the number increased from 1,000 to 3,000 cases within the last four years," he said during a news conference on Friday.

Hematopoietic stem cells are routinely used to treat a series of blood diseases, including leukemia and anemia, according to a leaflet published by the program.

The organization, established in 1992, has become the world's fourth-largest databank of stem cells donors, ranking after the United States, Germany and Brazil, with more than 1.5 million candidate donors listed in its database, Hong said.

"The number of candidate donors who had their blood samples enlisted in the program is expected to reach 2 million in 2015," he said.

The 3,000th donor was Ma Yahui, a 34-year-old woman from Northwest China's Xinjiang Uygur autonomous region, who had her blood extracted on Thursday at a hospital in Beijing. She received a certificate on Friday from the program with the number "3,000".

"I thought previously that donating stem cells is quite complicated, but I found out it is very simple after my blood was extracted yesterday," she said. "It's similar to donating blood."

The donated stem cells will be transplanted to a 2-year-old boy in South Korea who has leukemia, Ma said.

"I am a mother of a 4-year-old boy, and I felt deep sympathy toward the Korean baby patient," she said. "Saving the life of other people is not so difficultwhat we should do is just reach out our arms and give a little blood to the patients."

View original post here:
Eastday-Stem cell donors reaches 3,000 mark

Yet More Data on Body Weight and Medical Costs

A couple of generally useful large reference studies on body weight, level of exercise, and resulting life expectancy and lifetime medical costs have shown up in recent years. As I'm sure you all know by now, the data all points in the direction of more fat and less exercise correlating with a shorter, less healthy life and higher lifetime medical costs. Take a look at these items, for example:

I recently noticed another, similar study on the Israeli population:

Health care costs per person were calculated by body mass index (BMI) by applying Israeli cost data to aggregated results from international studies. These were applied to BMI changes from eight intervention programmes in order to calculate reductions in direct treatment costs. Indirect cost savings were also estimated as were additional costs due to increased longevity of program participants. Data on costs and Quality-Adjusted Life Years (QALYs) gained from Israeli and International dietary interventions were combined to provide cost-utility estimates of an intervention program to reduce obesity in Israel.

...

On average, persons who were overweight (25 ? BMI < 30)had health care costs that were 12.2% above the average health care costs of persons with normal or sub-normal weight to height ratios (BMI < 25). This differential in costs rose to 31.4% and 73.0% for obese and severely obese persons, respectively.

I imagine that the popularity of this sort of work of late, or at least the increased willingness of funding bodies to make the necessary grants, has to do with a greater awareness of the impending financial collapse in medical entitlements and centralized health systems. This sad end is somewhat inevitable whenever a system is set up such that patients do not bear costs directly and funds are drawn from taxed resources - there will be overspending, waste, spiraling prices, special interests and all the other ugly aspects of business as usual in politics.

The "solution" offered up by the talking heads is, as usual, more control over everything: rationing, expensive attempts to influence lifestyle choices, and so forth. A far better option, and one unlikely to be tried until these systems have decayed into the sort of wasteland commonly associated with the ruins left at the end of the Soviet era, is simply to let people buy and sell medical services unmolested, unregulated, and in open competition. But that offers those in power few opportunities to advance their own position and line their own pockets, so as you can imagine it doesn't have many advocates where it matters. But ultimately the money runs out and the promises cannot be kept; if something cannot be paid for then it will not be paid for, regardless of how pretty the lies and promises might be.

So two lessons here: firstly, don't get fat and don't stay fat. Secondly, don't expect anyone to be paying your way in later life, regardless of what government employees might have to say on the matter.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Nanog Reverses Some Aspects of Stem Cell Aging

It's been a while since nanog was discussed here; it's one of the genes associated with early efforts to reprogram somatic cells into stem cells and seems to be important in the activity of embryonic stem cells. Here researchers are investigating the reversal of stem cell aging: "Although the therapeutic potential of mesenchymal stem cells (MSC) is widely accepted, loss of cell function due to donor aging or culture senescence are major limiting factors hampering their clinical application. Our laboratory recently showed that MSC originating from older donors suffer from limited proliferative capacity and significantly reduced myogenic differentiation potential. This is a major concern, as the patients most likely to suffer from cardiovascular disease are elderly. Here we tested the hypothesis that a single pluripotency associated transcription factor, namely Nanog, may reverse the proliferation and differentiation potential of BM-MSC from adult donors. Microarray analysis showed that [expressing Nanog] markedly upregulated genes involved in cell cycle, DNA replication and DNA damage repair and enhanced the proliferation rate and clonogenic capacity of [adult] BM-MSC. Notably, Nanog reversed the myogenic differentiation potential and restored the contractile function of [adult] BM-MSC to a similar level as that of neonatal BM-MSC. ... Overall, our results suggest that Nanog may be used to overcome the effects of organismal aging on BM-MSC, thereby increasing the potential of MSC from aged donors for cellular therapy and tissue regeneration."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22949105

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Longevity in Mammals as an Ancient Phenomenon

An interesting view on the evolutionary depths of longevity in mammals, achieved through analysis of presently available genomes: "It is widely assumed that our mammalian ancestors, which lived in the Cretaceous era, were tiny animals that survived massive asteroid impacts in shelters, and evolved into modern forms after dinosaurs went extinct, 65 Mya. The small size of most Mesozoic mammalian fossils essentially supports this view. Paleontology, however, is not conclusive regarding the ancestry of extant mammals, because Cretaceous and Paleocene fossils are not easily linked to modern lineages. Here we use full-genome data to estimate the longevity and body mass of early placental mammals. Analysing 36 fully-sequenced mammalian genomes, we reconstruct two aspects of the ancestral genome dynamics ... Linking these molecular evolutionary processes to life history traits in modern species, we estimate that early placental mammals had a life-span above 25 years, and a body mass above one kilogram. This is similar to current primates, cetartiodactyls or carnivores, but markedly different from mice or shrews, challenging the dominant view about mammalian origin and evolution. Our results imply that long-lived mammals existed in the Cretaceous era, and were the most successful in evolution, opening new perspectives about the conditions for survival to the Cretaceous-Tertiary crisis."

Link: http://www.ncbi.nlm.nih.gov/pubmed/22949523

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

Cytokines in Sarcopenia, Obesity, and Immunosenescence

A recent open access paper points to changing cytokine levels as a candidate mechanism for a range of conditions that occur with age and are generally made either worse or more likely by the presence of excess fat tissue. The link between being overweight and a higher risk of suffering the common age-related conditions is well known; chronic inflammation is thought to be an important mechanism here due to the way in which it impacts so many different systems in our biology, but the exact details are still open to debate.

Sarcopenia, obesity, and natural killer cell immune senescence in aging: Altered cytokine levels as a common mechanism

An inevitable consequence of human and rodent aging is sarcopenia - loss of muscle mass. Some muscle loss is due to physical inactivity, but even highly trained athletes lose muscle mass and strength with age. Although exercise programs can prevent and/or ameliorate sarcopenia, the effectiveness of exercise interventions to build muscle and effect metabolic improvements is less efficient in elderly subjects than in the young, due to multiple cellular and biochemical changes. ... Adipose tissue gain also is very common in aging and is a growing health concern for all ages. Visceral (abdominal) fat is of the greatest health concern because it is associated with insulin resistance, type 2 diabetes, cardiovascular disease, dementia, cancer, and overall mortality. ... Furthermore, obesity prevents muscle gain in response to functional overload [and] the combination of obesity and sarcopenia (so-called sarcopenic obesity) carries high health risks.

Another hallmark of aging is declining adaptive immunity, with complex alterations in innate immunity. Immune senescence is associated with mortality from all causes, including infectious diseases. Natural killer (NK) lymphocytes are innate immune cells that control intracellular infectious agents and cancers. In contrast to T and B lymphocytes, NK cell number is relatively increased in healthy aging and defects in NK cell function are subtle. However, declining NK cell number or function in aging is associated with death in the elderly. Therefore, mechanisms that preserve NK cell number and function may promote healthy aging.

To relate sarcopenia, obesity, and declining immunity in aging, we speculated that these conditions are linked processes, which are controlled by adipose tissue-derived and skeletal muscle-derived cytokines, known as adipokines and myokines, respectively

You can't really control the degree to which your immune system has been and will be hammered by various common herpesviruses, such as the near-omnipresent cytomegalovirus, but do you have a great deal of control over the fat tissue end of the relationship proposed in this paper. Letting yourself go to seed, getting fat and unfit, has consequences in the long term: a shorter, less healthy life with higher medical bills. Maybe science and those medical costs will dig you out of this hole before it kills you, but why roll those dice if you don't have to? The future of aging, health, and the biotechnologies of rejuvenation on the horizon is already uncertain enough for those of us in middle age today. Every extra year you can gain might make the difference between taking advantage of the first therapies to reverse aging and missing that boat entirely.

Source:
http://www.longevitymeme.org/newsletter/latest_rss_feed.cfm

StemCells, Inc., Gunning for Another $10 Million from California Stem Cell Agency


Fresh from winning $40 million from the
California stem cell agency, StemCells, Inc., is shooting for
another, $10 million award from the state research effort.

The latest proposal comes as the
publicly traded firm also faces the task of raising $40 million that it
has promised the agency to match the earlier awards. That figure
could well rise to $50 million given the new application.
Martin McGlynn, CEO of the
well-connected Newark, Ca., firm, disclosed StemCells, Inc.'s,
latest proposal in an article by Catherine Shaffer in BioWorld. She
wrote,

“Already looking ahead, StemCells has
set its sights on one more CIRM initiative designed to fund early
stage clinical trials over a four-year period. StemCells has applied
for that grant, worth up to $10 million, to fund a Phase II trial in
PMD(Pelizaeus-Merzbacher disease).”

The article did not disclose the timing on the new application.
StemCells, Inc.'s lobbying efforts with the stem cell agency were vigorously aided by the former chairman of the $3 billion
California stem cell agency, Robert Klein (see here and here). And Wednesday evening, the company convinced
the state agency's board to overturn two successive reviewer rejections of a
$20 million proposal for Alzheimer's research. The vote was 7-5.
Klein's efforts came in a record-breaking round of appeals and emotional presentations by patient advocates, which triggered complaints from the board this week about "arm-twisting" and politicking. 
StemCells, Inc., was founded by the
eminent Stanford stem cell researcher Irv Weissman, who helped to
raise millions for the ballot initiative that created the stem cell
agency. He additionally appeared in in the campaign's TV advertising.
The campaign was headed by Klein, who ultimately raised $35 million
to convince voters to create the agency. Weissman is currently on the board
of the StemCells, Inc. His wife is executive vice president.
In July, the stem cell agency board
approved the first $20 million award to the firm for research involving spinal injury.
McGlynn told BioWorld,

"We're the only company that has
programs going on in all three regions of the central nervous system:
the brain, the spinal cord and the eye."

Not discussed in the BioWorld article
was a requirement, imposed by the CIRM board, that StemCells, Inc.,
show it can deliver $20 million in matching funds on the Alzheimer's
award before receiving any state funds. CIRM said no such board
requirement existed on the spinal award, but the firm has promised to
match the $20 million on that award as well.
BioWorld described the awards as
grants. In fact, they are loans. But under the terms of the loans, if
the research is not successfully commercialized, it will be
forgiven.  

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

Arm-twisting and Emotion: Stem Cell Directors Move to Reform Appeals on Multimillon Dollar Grants


Frustrated with politicking,
“arm-twisting,” lobbying and “emotionally charged
presentations,” the governing board of the $3 billion California
stem cell agency today approved short-term changes in its grant
appeal process and ordered up a study to prepare long-term reforms.

The moves followed a prolonged series of appeals on grant applications that began in July and continued through today,
setting records for the number of appeals and generating hours of
sometimes tearful and emotion-laden presentations from members of the
public.
The board adopted changes in the appeal process for its next few meetings that are aimed at curbing its
free-wheeling nature and making it more understandable to the public
and applicants. The board also directed creation of a panel to make
recommendations by the end of the year for more wide-ranging reforms.
Directors of the agency were clearly
not happy with the appeal process this summer. However, it has been a
problem since 2008 when Bert Lubin, now a director of the stem cell
agency and CEO of Childrens Hospital of Oakland, Ca., was the first applicant to make a public pitch before the board to overturn
reviewer rejection of his application.
One director, UCLA medical school dean,
Gerald Levey, said at the time,

"I don't think we can run a board
this way. If we do, it would be chaos." 

Today, CIRM Director Carmen Puliafito,
dean of the USC School of Medicine, said that “lots of lobbying”
was going over the last couple of months. He predicted there will
more lobbying and “more politicking.” Puliafito said,

“On big money grants, people will be
calling their friends.”

The name of former board chairman,
Robert Klein, was not mentioned during this afternoon's discussion.
But Klein vigorously and successfully backed an appeal (see here,
here and here) by StemCells, Inc., of Newark, Ca., for a $20 million
application that had been rejected twice by reviewers. Last night the
board approved the award on a 7-5 vote. It was the first time the
board has approved an award that was rejected twice by its reviewers.
Director Jeff Sheehy, co-vice chairman
of the review group and a communications manager at UC San Francisco,
said the agency is dealing with “big money grants” that are
“incredibly complex.” He also referred to “certain arm-twisting
by certain individuals.”
Several board members made references
to appearances by persons who have diseases or conditions that might
be affected by CIRM-financed research. Director Duane Roth, head of
CONNECT, a San Diego business development organization, said the
board is making decisions in “an emotionally charged setting.”
Other issues cited by directors include
the integrity of review process, fairness, consistency, shifting
appeals procedures, transparency and board discipline on appeals.

James Harrison, outside counsel to the board, said the board's action today includes "eliminating the reference to unpublished data in the discussion of 'material new information," imposing a 3-page limit on other correspondence, explaining that applicants should have seven business days from the time the (grants review group) recommendation is made available to them to file an (extraordinary petition), and posting all of the information regarding these policies in one place on CIRM’s website."

For a list of articles and CIRM
documents dealing with the appeal process, see here.

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

California Stem Cell Agency Okays $38 Million for Basic Research


Directors of the California stem cell agency today approved about $38 million for research into basic biology, including two appeals by researchers on applications initially rejected by reviewers.

The governing board turned down five appeals in the round, which attracted 357 applications in its "pre-app" process, 64 of which were invited to apply. Reviewers approved 25 applications.

The following appeals in the biology round were approved:

  • $1.3 million, Deborah Lieu of UC Davis. (Review summary here, appeal here.) 764
  • $1.4 million, Yanhong Shi  of the City of Hope. (See review summary here and appeal here.)

The board also approved another application that was rejected by reviewers based on a recommendation by CIRM President Alan Trounson.  It is very unusual for the board to approve rejected applications based on staff recommendations following a review. Trounson described the grant addressed a major bottleneck in stem cell science.

 The California stem cell agency is expected to post a press release shortly with the names of all recipients. The agency usually withholds names of applicants until the the board formally acts.
(An earlier version of this item reported that the board approved $37 million in grants.)

Source:
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Florida Researcher Wins $6.7 Million Grant to Come to Golden State


Dennis Steindler
UF Photo

The governing board of the California stem cell agency this morning approved a $6.7 million grant to recruit Dennis Steindler of the University of Florida to the Parkinson's Institute in Sunnyvale, Ca.

The grant was approved immediately following a 45-minute executive session with no further debate. (For more on this, see here, here and here.)

Steindler later told the California Stem Cell Report he would begin work in California as soon as possible.

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Board Concludes Private Session on Recruitment Grant


The governing board of the California stem cell agency has just concluded a 45 minute executive session on a $6.7 million grant to recruit a Florida scientist to the Parkinson's Institute in Sunnyvale, Ca.

It was the longest executive session ever on a recruitment grant, which are usually approved routinely with little serious discussion.

The board is now resuming discussion of the matter(see here and here.)

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Dennis Steindler Application: Excerpt from Review Summary


The CIRM summary of the review on the
$6.7 million grant to recruit Florida scientist Dennis Steindler to
the Parkinson's Institute in California carried a strong minority report. However, the review itself drew fire this morning from some CIRM board members.
They included patient advocate Jeff Sheehy, co-vice chair of the grant review group, who supported approval of the grant. He noted that the low score reflected two extreme opinions. He said some of the reviewers were doing their research on the Parkinson's Institute on the Internet during the actual review.  Sheehy said that was not a "good way" to perform a review and reflected a "major short-coming." 
Here is an excerpt from the review.

"In summary, this is an
application from an established leader in NSC biology to pursue
research focused on disease mechanisms in PD. Strengths of the
proposal include the quality of the PI, the focus of the project on
an interesting hypothesis, and the leadership in basic science that
the candidate would bring to the applicant institution. Weaknesses
included deficiencies in the research plan, the limited track-record
of the PI in PD research and an institutional environment lacking
adequate support for basic science investigations."

The summary continued, 

"During programmatic discussion some GWG (grant review group) members cited a need to broaden stem cell leadership not only at the
large universities but also at the smaller institutions as well. They
felt that the candidate's recruitment would strengthen the applicant
institution and provide leadership and strength in basic research.
The need for increased research focused on Parkinson's Disease was
also cited by some reviewers. A motion to recommend the application
for funding carried with a majority vote. Because more than 35% of
GWG members opposed the motion, opponents have exercised their right
to have that position reported to the ICOC. The consensus statement
from this group is as follows: 'Despite the facts that the
applicant has many excellent attributes, that Parkinson's disease is
a key area of interest, and that the applicant institution may
deserve additional consideration, our opinion is that the application
clearly falls short in several critical scientific areas that
outweigh the programmatic concerns and do not justify a
recommendation for funding. We believe that the people of California
depend upon us to make recommendations based on our scientific
expertise, for outcomes that are most likely to impact medicine and
the health and treatment of their citizens. We believe that their
money can be better spent.'"

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CIRM Board Eyes Florida Researcher for $6.7 Million Grant


The board of the California stem cell agency is discussing a proposal to award $6.7 million to recruit a Florida scientist to the Parkinson's Institute in Sunnyvale, Ca.

The scientist is Dennis Steindler of the University of Florida. The recruitment award received a score of 57, although the scores ranged from 30 to 75.  Jeff Sheehy, a member of the grant review group and CIRM board member, said the score reflected two extremely divergent positions by two reviewers.

The board has awarded four grants in its recruitment round over the past couple of years, but this is the first extended discussion of an award recommended by reviewers. It is also the first to have a representative of the applicant institution speaking publicly for the grant.

CIRM directors have now moved into executive session to discuss matters they prefer to air in private.

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Two Additional Appeals Rejected in Disease Team Round


The governing board of the California stem cell agency last night rejected appeals by two applicants -- OncoMed Pharmaceuticals of Redwood City and Albert Wong of Stanford -- in the $200 million disease team round.

Both petitions generated little discussion. You can find more on their petitions here and here.

The board also approved changes in its intellectual property and grant administration rules. Both proposals will now enter the state's official administrative law process for more comment and possible change.

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