Saturday, May 31, 2008

[StemCells] New Stem Cells for brain

May 31 2008, 12:48 AM EST

New stem cell therapy may aid the repair of damaged brains
EUREKALERT

Contact: Sean Wagner
swagner@wiley.com
781-388-8550
Wiley-Blackwell

According to some experts, newly born neuronal stem cells in the
adult brain may provide a therapy for brain injury. But if these stem
cells are to be utilized in this way, the process by which they are
created, neurogenesis, must be regulated.

A new study, led by Laurence Katz, Co-Director of the Carolina
Resuscitation Research Group at the University of the North Carolina
School of Medicine, suggests a way in which this might be achieved.

According to the research, neurogenesis can be regulated through
induced hypothermia. In rat subjects, a mild decrease in body
temperature was found to substantially decrease the proliferation of
newly-born neurons, a discovery that marks a major step forward for
the development of neuronal stem cell-based brain therapies.

Since the 1930s, brain damage from stroke, head injury, near drowning
and cardiac arrest was considered to be permanent because of a lack
of repair mechanisms like other parts of the body. However, discovery
of neuronal stem cells in the adult brain challenges that belief.

Many questions remain before we adequately understand how to control
these cells to repair a damaged brain, says Katz. However, the
findings represent an important step in demonstrating that these
cells can be controlled by simple external forces like hypothermia.

The presentation entitled Hypothermia Decreases Neurogenesis will be
given by Laurence Katz from The University of North Carolina School
of Medicine. This paper will be presented at the 2008 SAEM Annual
Meeting, Washington,D.C. on May 31, in the Neurovascular emergencies
forum beginning at 10 a.m. in Virginia Rooms A&B of the Marriott
Wardman Park Hotel. Abstracts are published in Vol. 15, No. 5,
Supplement 1, May 2008 of Academic Emergency Medicine, the official
journal of the Society for Academic Emergency Medicine.

###

Press Room 2008 SAEM Annual Meeting, May 29-June 1, 2008,Washington,
D.C.
Location Park Tower Suite #8229
Chicago, IL
Tel: (202) 328-2000 (ask for the SAEM Registration Desk)
Fax: (202) 234-0015 (mark for attn of [Maryanne Greketis or Sandra
Rummel])

Contact Sean Wagner (swagner@wiley.com) to arrange for an interview
prior to or during the SAEM Annual Meeting. Dr. Katz can be reached
directly at lkatz@med.unc.edu.

About The Society for Academic Emergency Medicine (www.saem.org)

The Society for Academic Emergency Medicine (SAEM) is a national non-
profit organization of over 6,000 academic emergency physicians,
emergency medicine residents and medical students. SAEM's mission is
to improve patient care by advancing research and education in
emergency medicine. SAEM's vision is to promote ready access to
quality emergency care for all patients, to advance emergency
medicine as an academic and clinical discipline, and to maintain the
highest professional standards as clinicians, teachers, and
researchers. The SAEM Annual Meeting attracts approximately 2,000
medical students, residents and academic emergency physicians. It
provides the largest forum for the presentation of original research
in the specialty of Emergency Medicine.

About Academic Emergency Medicine (www.aemj.org)

AEM is a peer-reviewed journal whose goal is to advance the science,
education, and clinical practice of emergency medicine, to serve as a
voice for the academic emergency medicine community, and to enhance
the goals and objectives of the Society for Academic Emergency
Medicine (SAEM). Members and non-members worldwide depend on this
journal for translational medicine relevant to emergency medicine, in
addition to clinical news, case studies and more.

About Wiley-Blackwell

Wiley-Blackwell was formed in February 2007 as a result of the
acquisition of Blackwell Publishing Ltd. by John Wiley & Sons, Inc.,
and its merger with Wileys Scientific, Technical, and Medical
business. Together, the companies have created a global publishing
business with deep strength in every major academic and professional
field. Wiley-Blackwell publishes approximately 1,400 scholarly peer-
reviewed journals and an extensive collection of books with global
appeal. For more information on Wiley-Blackwell, please visit
www.blackwellpublishing.com or http://interscience.wiley.com.

http://www.genengnews.com/news/bnitem.aspx?name=36543325

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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[StemCells] CB & Stroke

Help for simulation-tools and stroke patients

Jörg Willems has made an important contribution to our understanding
of multi-scale problems in fluid mechanics and thermodynamics. The
effects of a stroke can now be significantly alleviated with a stem
cell therapy based on umbilical cord blood.

Simulation is an important tool for computer-based development and
pretesting of materials, helping eliminate expensive, dangerous
mistakes. Computer-based testing is a specialized field of the
Fraunhofer Institute for Industrial Mathematics ITWM in
Kaiserslautern, not least because materials simulation is a complex
process involving a great deal of mathematics. This is especially
true of multiscale materials modeling, the mathematical description
of materials across multiple spatial and time scales. Graduate
mathematician Jörg Willems has significantly improved our
understanding of multiscale problems associated with flow dynamics
and thermodynamics. His diploma thesis has greatly facilitated the
use of numerical simulation in the development of filter media,
insulating materials, composite materials and fuel cells. He has been
awarded 2nd place in the Hugo Geiger Prize for his work.

When a stroke is diagnosed, every minute is of high value for
limiting its impact. Existing treatment protocols only take effect
after three to four hours. Physicians are therefore looking for
effective alternatives such as stem cell therapy. Johannes Boltze of
the Fraunhofer Institute for Cell Therapy and Immunology IZI in
Leipzig is one of them. In his doctoral thesis he established a model
for examining strokes in rats, and managed to show that treatment
with stem cell containing populations shows promising results: "The
ability of untreated animals to move after the infarct is severely
impaired," explains Johannes Boltze. "In behavioural tests, for
instance, they have difficulty balancing well enough to run across a
bar. Not so in the case of the animals we treated with cells. They
nimbly run across again after only a fortnight." The stem cells
promote endogenous healing and organizational processes in the brain.
As a result, the surviving nerve cells are probably more resistant to
the damage if the treatment is begun within 72 hours after stroke
onset. Thus, cells from umbilical cord blood and bone marrow could be
used for the stroke trials – an uncontroversial method that avoids
any ethical concerns. The cell therapy procedure is ideal for further
clinical usage in a stroke unit. Dr. Johannes Boltze received the 3rd
place in the Hugo Geiger Prize for his research work.-Fraunhofer-
Gesellschaft

Submitted by harminka on Fri, 2008-05-30 13:24.
http://www.huliq.com/60770/help-simulationtools-and-stroke-patients

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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[StemCells] April 10, 2008 FDA Embryonic Info Online

Transcripts, powerpoint and more available at FDA.gov . Search box is
in upper right corner.

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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[StemCells] SCs for Drugs

How to make a science out of drug discovery
Canada really needs a national drug development niche
Last Updated: Friday, May 30, 2008 | 9:04 AM ET Comments3Recommend2By
Stephen Strauss CBC News
Apparently one of the greatest mysteries in science is how to make a
science out of drug discovery.

Let me refer you off the top to Aled Edwards and his blistering
critique of today's drug development procedures: "What is crippling
the development of new medicines is the fact that as we discover
potential new medicines and we start to test them in people, 90 per
cent fail.

"And the 90 per cent fail not because scientists are dumb or they
make mistakes," Edwards, who is head of collaboration between the
University of Toronto, the University of Oxford, and Sweden's
Karolinska Institute called the Structural Genomics Consortium,
recently told me. "They fail because we have a very poor
understanding of human physiology or pharmacology. We just don't
know. You could put 82 eggheads in a room, each with eight Nobel
Prizes each, and give them 10 medicines and say 'which one is going
to work in a person' - and none would be able to predict."

Ouch — but the blistering continues.

"The pharmaceutical industry is less productive every year and has
been for the last three decades," he says. "People make chairs more
productively, hamburgers more productively, cars more productively,
everything else in the world except medicines.

"And it's not a problem with the industry and the structure of
industry and the structure of biotechnology or academia. It's that we
don't understand human disease, and until we get that done, we ain't
gonna make medicines better."

'People make chairs more productively, hamburgers more productively,
cars more productively, everything else in the world except
medicines.'
— Aled EdwardsThis is not just one basic scientist's reveling in
hyperbole.

In 2004, the U.S. Food and Drug Administration dropped a bomb on the
pharmaceutical world in a report entitled Innovation or Stagnation.
It suggested that while U.S. biomedical research funding had gone to
$94 billion in 2003 from $37 billion US in 1994 (a 57 per cent
increase when inflation was taken into account), a new drug entering
early stage clinical trials had only an 8 per cent chance of reaching
market.

This was down from 14 per cent about 15 years before. The year 2004
represented a 20-year low in the numbers of new molecular therapies -
truly new drugs reaching market. Failure rates during final-stage
clinical trials were as high as 50 per cent, up from 20 per cent a
decade before.

All this is within the context of the fact that the cost of getting a
drug to market is somewhere between $800 million US and $1.7 billion.
The report pointed out if you could weed out 10 per cent of likely
failures before they enter clinical trials it would save companies
$100 million per drug.

What to do to make the system more rational?

Well, Edwards and his Swedish and English collaborators are studying
the shapes of the body's proteins and then making their results
freely available on the internet. It turns out the shape of proteins
is vital knowledge when trying to develop a drug to block the actions
of some disease causing body molecule. And their view is that this is
knowledge that all companies need to have for free as a precursor to
drug development.

Their analysis suggests they can reduce early drug discovery time by
as much as 18 months and do the work at anywhere from a third to an
eighth of the price of traditional academic and industrial research.

I like the sound of that, but also fear that things will still get
stuck later on. And indeed, the U.S. Food and Drug Administration
(FDA), when it looked at the problem, came up with at least six
sticking points in the U.S. for rational and efficient drug
development.

To my mind, the biggest problem is that even though drug companies
have invested billions in trying to make their process more
efficient, they are not in the business of unplugging the entire
system. Au contraire. If they come up with, say, a cellular assay
that lets them choose potential drug winners from losers earlier, it
is actually in their financial interest to keep this information from
potential competitors. They want their rivals to be inefficient.

Perhaps equally important, they aren't in the "selling-a-more-
efficient-process" business. They're drug companies, after all. They
want a $5 billion-a-year "treatment" for male impotence and not a
bundle of assays or imaging technology to make the whole process
better for everyone.

Which leads me in a rather roundabout way to a national pitch.

Canada as a country is great at medical research - per capita we're
right at the top in the world - but we ain't so great at turning
those drugs into products. Sure, there was insulin and the three-drug
cocktail for AIDS, but the reality is that we are a branch-plant
economy for foreign drug companies. And this is extremely worrying in
an age when the best future jobs are seen to be in places like
biomedicine and not, um, well, car plants in Ontario or clothes-
manufacturing plants in Quebec.

A few places in this country - Montreal, the new MaRS facilities in
Toronto, Vancouver, Alberta, Nova Scotia, Saskatchewan and even
little Prince Edward Island - understand this and have tried to
create what are called bioclusters. These are centres of excellence
that integrate research and industry. But the truth is there are
dozens and dozens and dozens of these bioclusters in every developed
and developing country around the world. If we were a relentlessly
entrepreneurial country we might forge ahead, but well, again, we
ain't.

So what I think Canada really needs is a national drug development
niche.

OK, maybe the earliest of the drug development stuff is best left to
Open Access, a la Edwards's model, but we could make it our national
calling to nourish companies that specifically try to improve the
rational discovery process down the pipeline: companies that try to
come up with things like heart stem cells you can test drugs on to
see if they might ultimately cause heart damage, or new kinds of
imaging technology to watch how living human cells respond to
treatment and how living animals experience them.

Take aim at the boring middle ground of rational drug development and
not the sexy billion-dollar final product. That won't be easy.

"Convincing scientists that an assay has a commercial value is tough,
and patenting an assay is very tough," Mark Poznansky, former
president and scientific director of the Robarts Research Institute
in London, Ont., recently warned me when I ran the idea past him.

Nonetheless, it seems to me in a highly competitive world where good
jobs slip away in a blink, Canada needs to mark out a patch of
medical research and say, "This is us. This is our national
expertise. And we're betting this is where our biomedical BlackBerry
will come from."

http://www.cbc.ca/technology/story/2008/05/30/f-strauss-
drugresearch.html

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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[StemCells] France & clinical trials

France: A leader in clinical trials

Clinical trials are a vital element of the pharmaceutical industry,
in which France is considered the best in Europe. Its expertise is
derived from several decades of collaboration with hospitals and
partners involved with French health sector..
CJ: The French Technology Press Office, Ubifrance, New Delhi,
India , 1 day ago Views:183 Comments:0
GLOBAL REVENUES of medical and pharmaceutical research are increasing
at the rate of 20 per cent , reaching a market size of US$ 15.4
billion in 2006. Companies look at France as the centre of excellence
for medical and pharmaceutical research, since the performance of
clinical trials in specialist hospitals is a key stage in the
treatment process.

Swiss pharmaceutical laboratory Novartis, for example, employs nearly
2,700 people in France, of which over 200 are dedicated to
international clinical trial programmes. Expertise in this field is
derived from several decades of collaboration with hospitals and the
various partners involved with the French health sector.

Alongside prestigious French contract research organisations are the
leading global clinical trial companies like Covance, Parexel, MDS
Pharma, and the US company Quintiles. The US company is the number
one in the industry and employs 600 people in France in two
locations - Paris and Strasbourg.

The quality of the clinical trials is what attracted biotechnology
company Myosix, a subsidiary of the US company Genzyme, which has
developed a particularly innovative technique for the growth of adult
muscle stem cells.

The creation of CeNGEPS - the national centre for managing clinical
trials, in Lyon, will play a key role in facilitating the
administrative organisation of clinical trials in the industry. The
government supports eight competitiveness clusters dedicated to life
sciences, which bring the various players together to work in a
climate of innovation. In addition, the pharmaceutical industry
benefits from the best research and development (R&D) tax credit
system in Europe, which reimburses 50 per cent of R&D costs in the
first year.

Clinical trials, a high value-added sector that is crucial for the
pharmaceutical industry, require cooperation between industry,
research laboratories, medical practitioners and service providers.
The efficient environment and high-quality technical facilities
created by France are assets for pharmaceutical companies that expect
successful results.

According to Philippe Favre, president of 'Invest in France Agency',
The French pharmaceutical market is the biggest in Europe and the
third-largest in the world. Its attractiveness is linked to the
quality of Frances healthcare system, recognised as one of the best
in the world by the World Health Organisation and the French hospital
system, which is number one in Europe.

Invest in France Agency (IFA) promotes and facilitates international
investment in France. The IFA network operates worldwide. It works in
partnership with regional development agencies to offer business
opportunities and customised services to international investors all
over France.

http://www.merinews.com/catFull.jsp?articleID=134916

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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Friday, May 30, 2008

[StemCells] Stopping Cancer AND turning mature to SC

May 15, 2008

Adult Cells Steal Trick from Cancer to Become Stem Cell-Like
A route used by tumor cells to spread could be exploited to make stem
cells for regenerative medicine and cancer therapies
By Nikhil Swaminathan

In a boon to cancer treatment and regenerative medicine, scientists
have discovered that a trick used by tumor cells that allows them to
migrate around the body can cause normal, adult cells to revert into
stem cell–like cells.

Large quantities of these reverted cells could be used to treat
anything from spinal cord injury to liver damage without the risk of
tissue rejection, said Robert Weinberg, a biologist at the
Massachusetts Institute of Technology's Whitehead Institute for
Biomedical Research and co-author of a study appearing in Cell.
Learning more about how cancer cells move around the body is also
providing scientists with new insights that could thwart the spread
of the disease.

The key to the process is a better understanding of developmental
changes in the body's two primary cell types: epithelial cells (those
that constitute the skin and most internal organs) and mesenchymal
cells (which make up connective tissue). The key difference between
the two cell categories is that epithelial cells adhere very tightly
to one another, making sheetlike layers, whereas mesenchymal cells
are only loosely bound and can migrate within the body. In the
developing embryo, an initial group of epithelial cells undergoes a
shift called an "epithelial to mesenchymal transition" (EMT) to form
bones, blood and cartilage as well as the heart.

Likewise, some cancerous cells can perform a temporary EMT
transformation to the mobile mesenchymal form. The conversion
improves the cells' tumor-forming ability, cutting the number of
tumor cells required to form a carcinoma from one million to just
10,000, the researchers say.

"More than 80 percent of cancer in humans occurs in epithelial
cells," says study co-author Sendurai Mani, an assistant professor of
molecular pathology at the University of Texas' M.D. Anderson Cancer
Center in Houston and a former postdoc in Weinberg's lab. Previous
work in Weinberg's lab had shown that after a tumor forms in one part
of the body, some of the cancer cells undergo EMT, Mani explains. The
now-mesenchymal cells can then travel to a remote site, where they
eventually convert back to their epithelial state and clump together
into a secondary tumor.

Working with human breast tissue, the new study's authors attempted
to induce EMT in normal cells; they figured they would just get
fibroblasts, a type of connective tissue that is important in wound
healing. When they looked closely, however, they noted that the
transformed cells had surface proteins that were common to stem
cells. Cultured in the lab, the changed cells showed an ability to
differentiate into (or become) two discrete cells found in breast
tissue. And the transformed cells proved to be very similar to actual
stem cells from both mice and humans.

"What we're doing is inducing dedifferentiation," Mani says. He noted
that it's not yet clear how far these cells can go down the path to
immaturity—and, with it, the ability to become any tissue in the
body. "We found, surprisingly, that EMT and stem cells could be
linked; we show that, yes, they are very closely linked."

Mani says that the scientists may next pursue two paths: The team can
determine how to stop cancer cells from undergoing this
transformation in the first place. Second—a path they are already
pursuing—they can gauge these transformed adult cells' worth as stem
cell surrogates for regenerative medicine.

As far as the promise of regenerative therapies, the team will
attempt to determine just how stem cell–like these cells are by
inducing EMT in epithelial cells from the mammaries of mice to see if
they can grow a breast in the lab. If they succeed, they can be
reasonably confident that epithelial cells can be taken from a
patient and used to regenerate damaged tissue in that same person.

http://www.sciam.com/article.cfm?id=adult-cells-steal-trick-f

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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[StemCells] Slowing ALS - Marrow SCs

Media Release | May 26, 2008
Vancouver Researchers Pioneer Safe Pathway to Slow ALS Using Stem
Cells
A unique pilot study has established a safe pathway for using bone-
marrow stem cells to slow down and potentially treat Amyotrophic
Lateral Sclerosis (ALS), a fatal neurodegenerative disease without
cure.

The study, published in the journal, Muscle & Nerve and led by Dr.
Neil Cashman, professor of neurology at The University of British
Columbia and director of the ALS program at Vancouver Coastal Health
and VCH Research Institute, tested the use of a growth factor
stimulant in ALS patients and found that bone-marrow stem cells
became activated with no adverse effects to patients.

"Our idea was to use a growth factor stimulant to increase the number
of circulating stem cells from within the body's bone marrow where
they would have the potential to travel to the site of injury and
begin repair, slowing down the progression of ALS," says Cashman, who
also holds the Canada Research Chair in Neurodegeneration and Protein
Misfolding Diseases at UBC and is a member of the Brain Research
Centre at UBC Hospital.

"This pathway, if one day successful, may provide a new therapy that
will avoid the ethical debate surrounding embryonic stem cells," says
Cashman.

Growth factors are proteins that can stimulate cell division. They
occur naturally in the human body and can also be developed in a
laboratory. Stem cells serve as a "repair system" in the human body
and have the potential to develop and divide into many different cell
types.

"The project was complex because growth factors have the potential to
activate the wrong cells in the brain and spinal cord, which could be
harmful to ALS patients" says Cashman.

The researchers identified Granulocyte Colony Stimulating Factor (G-
CSF) as the safest possible growth factor to use. They then conducted
the pilot trial to establish safety and measure stem cell
mobilization.

"We were able to measure a prominent effect on stem cell mobilization
and found no adverse effects in the patients," said Cashman. "There
have been many misgivings in using stem cell stimulators in ALS
patients but now we know we can safely do this. This is an important
first step in providing a new treatment for ALS."

The research team is now developing a larger scale multicentre trial
to look at therapeutic effect. This trial is at least one year away
from beginning.

ALS is a progressive and ultimately fatal neurodegenerative disease
that produces weakness, atrophy – partial or complete wasting away of
a part of the body, and spasticity – continuous contracting of
certain muscles. It results from progressive degeneration of motor
neurons in the brain, brainstem, and spinal cord. There is no cure
for ALS and to date the only registered pharmacological treatment is
riluzole, which slows the progression of the disease on average by 10-
15 per cent. New effective therapies are greatly needed to slow or
halt this disease.

The Webster Foundation in Montreal through the VGH & UBC Hospital
Foundation in Vancouver, as well as the Temerty Family Foundation in
Toronto provided funding for this study. The co-authors include Dr.
Andy Eisen (senior author), professor Emeritus, Neurology, University
of British Columbia and former director Vancouver Coastal Health ALS
program; and Dr. Charles Krieger, associate professor of
kinesiology, Simon Fraser University, professor, neurology, clinical
associate professor, Neurology, University of British Columbia, and
clinician researcher VCH ALS program.

VCHRI is the research body of Vancouver Coastal Health Authority. In
academic partnership with UBC, the institute advances health research
and innovation across B.C., Canada, and beyond. www.vchri.ca

The Faculty of Medicine at UBC provides innovative programs in the
health and life sciences, teaching students at the undergraduate,
graduate and postgraduate levels, and generates more than $200
million in research funding each year.

The Brain Research Centre at UBC Hospital is a multidisciplinary
centre dedicated to improving understanding and finding new
treatments for brain diseases. The centre is a partnership of the
University of British Columbia and Vancouver Coastal Health Research
Institute.

- 30 -
Contact
Catherine Loiacono
UBC Public Affairs
Tel: 604.822.2644
Cell: 604.209.3048
E-mail: catherine.loiacono@ubc.ca

Lisa Carver
VCHRI Communications
Tel: 604.875.4111, loc. 61777
Cell: 604.319.7533
E-mail: lisa.carver@vch.ca




Last reviewed 29-May-2008
http://www.publicaffairs.ubc.ca/media/releases/2008/mr-08-061.html

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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[StemCells] iPS provide new insights to cellular reprogramming

New insights into cellular reprogramming revealed by genomic analysis
30.05.2008
Research collaboration of Harvard, Whitehead Institute, and Broad
Institute uncovers critical molecular events underlying reprogramming
of differentiated cells to a stem cell state

The ability to drive somatic, or fully differentiated, human cells
back to a pluripotent or "stem cell" state would overcome many of the
significant scientific and social challenges to the use of embryo-
derived stem cells and help realize the promise of regenerative
medicine.

Recent research with mouse and human cells has demonstrated that such
a transformation ("reprogramming") is possible, although the current
process is inefficient and, when it does work, poorly understood. But
now, thanks to the application of powerful new integrative genomic
tools, a cross-disciplinary research team from Harvard University,
Whitehead Institute, and the Broad Institute of MIT and Harvard has
uncovered significant new information about the molecular changes
that underlie the direct reprogramming process. Their findings are
published online in the journal Nature.

"We used a genomic approach to identify key obstacles to the
reprogramming process and to understand why most cells fail to
reprogram," said Alexander Meissner, assistant professor at Harvard
University's Department of Stem Cell and Regenerative Biology and
associate member of the Broad Institute, who led the multi-
institutional effort. "Currently, reprogramming requires infecting
somatic cells with engineered viruses. This approach may be
unsuitable for generating stem cells that can be used in regenerative
medicine. Our work provides critical insights that might ultimately
lead to a more refined approach."

Previous work had demonstrated that four transcription factors —
proteins that mediate whether their target genes are turned on or
off — could drive fully differentiated cells, such as skin or blood
cells, into a stem cell-like state, known as induced pluripotent stem
(iPS) cells. Building off of this knowledge, the researchers examined
both successfully and unsuccessfully reprogrammed cells to better
understand the complex process.

"Interestingly, the response of most cells appears to be activation
of normal `fail safe' mechanisms", said Tarjei Mikkelsen, a graduate
student at the Broad Institute and first author of the Nature
paper. "Improving the low efficiency of the reprogramming process
will require circumventing these mechanisms without disabling them
permanently."

The researchers used next-generation sequencing technologies to
generate genome-wide maps of epigenetic modifications — which control
how DNA is packaged and accessed within cells — and integrated this
approach with gene expression profiling to monitor how cells change
during the reprogramming process. Their key findings include:

Fully reprogrammed cells, or iPS cells, demonstrate gene expression
and epigenetic modifications that are strikingly similar, although
not necessarily identical, to embryonic stem cells.

Cells that escape their initial fail-safe mechanisms can still
become `stuck' in partially reprogrammed states.

By identifying characteristic differences in the epigenetic maps and
expression profiles of these partially reprogrammed cells, the
researchers designed treatments using chemicals or RNA interference
(RNAi) that were sufficient to drive them to a fully reprogrammed
state.

One of these treatments, involving the chemotherapeutic 5-
azacytidine, could improve the overall efficiency of the
reprogramming process by several hundred percent.

"A key advance facilitating this work was the isolation of partially
reprogrammed cells," said co-author Jacob Hanna, a postdoctoral
fellow at the Whitehead Institute, who recently led two other
independent reprogramming studies. "We expect that further
characterization of partially programmed cells, along with the
discovery and use of other small molecules, will make cellular
reprogramming even more efficient and eventually safe for use in
regenerative medicine."

Nicole Davis | Quelle: EurekAlert!
Weitere Informationen: www.broad.mit.edu
www.harvard.edu
www.wi.mit.edu

http://www.innovations-
report.de/html/berichte/biowissenschaften_chemie/bericht-111173.html

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StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
____________________________________________
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[StemCells] 'Remarkable results' for SC limb ichemia trials

Participants in TCA Cellular Therapy's Stem Cell Protocol
Experiencing Remarkable Results
Posted on: Thursday, 29 May 2008, 18:00 CDT

Participants in a Federal Drug Administration (FDA) protocol at TCA
Cellular Therapy utilizing stem cells to treat lower limb ischemia
are experiencing increased mobility and decreased pain in lower legs.

Lower limb ischemia is a condition where plaque build-up causes
decreased circulation in the lower leg. Symptoms of the condition
include intense pain and swelling.

Study participants may have had different factors that contributed to
their condition: a family history of Peripheral Artery Disease (PAD),
history of smoking and other vascular conditions. Common among them
however, were that more traditional treatments (utilizing stents and
grafts) were ineffectual and that the patients were losing their
ability to continue their daily activities.

Meryl Sharp was an avid gardener before she had to give up the hobby
last year. She could no longer walk the length of the lawn without
stopping to rest her throbbing legs. "It got to the point where the
intervals of rest were not even enough to ease the pain," she said.

The study participants were referred by their vascular surgeons to
TCA Cellular Therapy, where Gabriel Lasala, M.D. and Jose Minguell,
Ph.D. have been authorized by the FDA to study the safety and
efficacy of stem cell therapy for lower limb ischemia.

"The similarity in the recovery of our patients is promising," said
Dr. Lasala. "We find that the stem cells, once re-injected, go about
forming new blood vessels, thus increasing circulation dramatically."

Drs. Lasala and Minguell have developed a treatment where a patient's
own stem cells are taken from the hip, grown in a sterile environment
and then re-infused into 38 areas of the leg.

So far, ten patients have received the stem cell treatment for
peripheral vascular disease.

"Patients are experiencing increased mobility within weeks of their
infusions. The continued improvement throughout their recoveries is a
positive sign," Lasala said.

Carleton Wert could only walk 2 1/2 minutes on the treadmill before
he underwent the stem cell therapy. At his three week check-up, he
clocked 4 minutes. Within two months, his time improved to over 10
minutes.

Similarly, Michael Pearl could not even undergo the treadmill test
prior to his infusion in mid-November because his pain was so
intense. He went from walking 5 minutes at his one-month check-up to
18 minutes at the three-month mark.

With increased mobility, Dr. Lasala's patients are resuming their
normal routines. Wert, who was on disability because of the ischemia,
is now seeking employment. Sharp has gone back to gardening, creating
a new antique garden with her husband in their front yard.

Perhaps most striking is the transformation experienced by Penny
Kibideaux. Running out of options to treat her ischemia, Kibideaux
had already scheduled a leg amputation. Under the advice of her
physician, Kibideaux went to see Dr. Lasala. Not only has he saved
her leg, Kibideaux says he has saved her life. Just weeks after her
November infusion, she walked several shopping malls as part of her
Christmas shopping. She has also recently taken up line dancing.

The FDA protocol study will continue for the next two years, after
which Dr. Lasala expects that stem cell treatment for lower limb
ischemia will be widely utilized in the medical community.

"We are excited that our patients are responding well to the
treatment," he said. "We hope that more people will be able to
experience relief and improve their quality of life through this
procedure."

About TCA Cellular Therapy:

TCA Cellular Therapy is the only private company in the United States
that is participating in FDA protocols related to stem cell research.
Under the direction of Medical Director Gabriel Lasala, M.D. and
Scientific Director Jose Minguell, Ph.D., TCA Cellular Therapy is
undergoing pioneering research with stem cell therapy for limb
ischemia. Its affiliated company, LifeSource Cryobank, LLC is a
privately-owned, FDA registered, state of the art laboratory
committed to ensuring the safety and integrity of stem cells derived
from both umbilical cord blood and adult bone marrow in a totally
secure environment. Both companies are located in Covington,
Louisiana.

Source: Business Wire

More News in this Category

http://www.redorbit.com/news/health/1408668/participants_in_tca_cellul
ar_therapys_stem_cell_protocol_experiencing_remarkable/

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¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯¯
StemCells subscribers may also be interested in these sites:

Children's Neurobiological Solutions
http://www.CNSfoundation.org/

Cord Blood Registry
http://www.CordBlood.com/at.cgi?a=150123

The CNS Healing Group
http://groups.yahoo.com/group/CNS_Healing
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