Stem Cell: May 2008

Saturday, May 31, 2008

Keyword News: [stem cell]

Yahoo! Alerts

Saturday, May 31, 2008 11:31 PM PDT

Human Stem Cell Line Made Containing Sickle Cell Anemia Mutation
Science Daily Sat, 31 May 2008 7:13 AM PDT
Researchers at Johns Hopkins have established a human cell-based system for studying sickle cell anemia by reprogramming somatic cells to an embryonic stem cell like state. Publishing online on May 29, the team describes a faster and more efficient method of reprogramming cells that might speed the development of stem cell therapies.

Local stem cell firm gets fed grant
The Capital Times Sat, 31 May 2008 10:28 AM PDT
Madison-based stem cell company Stemina Biomarkers Discovery Inc. has learned it will receive a $150,000 Phase I grant from the National Cancer Institute through the federal government's Small Business Innovation Research grant program, the Wisconsin Technology Council said in a news release Friday. Stemina, founded in late 2006 by chief executive officer Beth Donley and UW-Madison stem cell ...

Stem cell hope for blind dad
The Courier Mail Sat, 31 May 2008 7:00 AM PDT
A BRISBANE dad who has optic atrophy has regained his sight after receiving controversial embryonic stem-cell treatment in India. It reversed 15 years of degradation.

New stem cell therapy may help repair injured brains
New Kerala Sat, 31 May 2008 3:23 AM PDT
Washington, May 31: Researchers at the University of the North Carolina School of Medicine have found that hypothermia, a condition in which an organism's temperature drops below that required for normal metabolism and bodily functions, may help in the development of neuronal stem cell-based brain therapies.

New Stem Cell Therapy May Aid The Repair Of Damaged Brains
Science Daily Sat, 31 May 2008 6:26 AM PDT
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.

New stem cell therapy may aid the repair of damaged brains
New Kerala Sat, 31 May 2008 1:32 AM PDT
Washington, May 31 : Just born neuronal stem cells in an adult brain may have the potential to repair injuries that the brain might sustain.

ViroPharma completes enrollment in phase 3 study of maribavir
PharmaBiz Sat, 31 May 2008 0:42 AM PDT
ViroPharma Incorporated has completed enrolment in its pivotal phase II study of maribavir in stem cell transplant patients.

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[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] 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] 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] 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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Friday, May 30, 2008

Keyword News: [stem cell]

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Friday, May 30, 2008 11:31 PM PDT

Researchers Develop Stem Line With Sickle Cell Mutation
MedicineNet.com Fri, 30 May 2008 12:30 PM PDT
Title: Researchers Develop Stem Line With Sickle Cell Mutation Category: Health News Created: 5/30/2008 2:00:00 AM Last Editorial Review: 5/30/2008

Brazil's Top Court Approves Stem Cell Research
Channel 8 San Diego Fri, 30 May 2008 8:07 AM PDT
Brazil's Supreme Court ruled Thursday that scientists can conduct embryonic stem cell research, which holds the promise of curing Parkinson's disease and diabetes but raises ethical concerns about the limits on human life.

Johns Hopkins Researchers Develop Human Stem Cell Line Containing Sickle Cell Anemia Mutation
BioresearchOnline Fri, 30 May 2008 6:48 AM PDT
Researchers at Johns Hopkins have established a human cell-based system for studying sickle cell anemia by reprogramming somatic cells to an embryonic stem cell like state

Johns Hopkins Researchers Develop Human Stem Cell Line Containing Sickle Cell Anemia Mutation
Medical News Today Fri, 30 May 2008 6:13 AM PDT
Researchers at Johns Hopkins have established a human cell-based system for studying sickle cell anemia by reprogramming somatic cells to an embryonic stem cell like state. Publishing online in Stem Cells on May 29, the team describes a faster and more efficient method of reprogramming cells that might speed the development of stem cell therapies.

Viropharma Announces Completion Of Enrollment In Phase 3 Study Of Maribavir In Stem Cell Transplant Patients
Medical News Today Fri, 30 May 2008 4:13 AM PDT
ViroPharma Incorporated (Nasdaq: VPHM) announced that it completed enrollment in its pivotal Phase 3 study of maribavir in stem cell transplant patients.

Brazil's Top Court Approves Stem Cell Research
The Christian Post Fri, 30 May 2008 5:45 AM PDT
Brazil's Supreme Court ruled Thursday that scientists can conduct embryonic stem cell research, which holds the promise of curing Parkinson's disease and diabetes but raises ethical concerns about the limits on human ...

Stem Cell Therapeutics Corp. Expands Executive Team by Appointing Thomas Franck as Vice President of Commercial Planning
Marketwire via Yahoo! Finance Fri, 30 May 2008 4:30 AM PDT
Stem Cell Therapeutics Corp. is pleased to announce the appointment of Mr. Thomas Franck as Vice President of Commercial Planning.

Brazil says yes to stem cell research — again
SciDev.net Fri, 30 May 2008 10:15 AM PDT
Brazil's Supreme Federal Court voted by a narrow margin to uphold legislation allowing research on embryonic stem cells yesterday (29 May), after almost three years of deadlock.

Brazilian supreme court rules to approve embryonic stem cell research
People's Daily Fri, 30 May 2008 1:35 AM PDT
Brazil's Federal Supreme Court Thursday ruled to uphold a 2005 law allowing research into embryonic stem cells in the country. The ruling rejected a petition by a group of congress members who questioned the legitimacy of the law an ...

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HSCI Research Newsletter

Harvard Stem Cell Institute Research Newsletter

RESEARCH COMMENTARY

SPOTLIGHT ARTICLE

REVIEW and COMMENTARY ARTICLES

SCIENTIFIC PAPERS

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cancer

cell biology

developmental biology

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imaging

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This HSCI Research Update synthesizes the scientific work published by HSCI Principal Faculty each month. To continue receiving this newsletter, please register as an HSCI Affiliate or Friend by clicking here.

If you are having problems viewing this newletter, click here to view it in your web browser.

Research Commentary:

Genomic approaches provide insights into the molecular basis of pluripotency

Spotlight Article:

Dissecting direct reprogramming through integrative genomic analysis

Research Commentary

Genomic approaches provide insights into the molecular basis of pluripotency

by Lisa Girard, PhD
HSCI Science Editor

Nuclear reprogramming demonstrates the potential for reversability in cellular differentiation. Reprogramming introduces a small number of transcription factors into somatic cells, such as skin cells, transforming the skin cells into induced pluripotent stem cells (iPS), While a core set of factors necessary for reprogramming has been identified the process is extremely inefficient (less than .1% of cells exposed to factors are transformed). The impetus to improve the efficiency of reprogramming is high. Approaches in regenerative medicine, such as replacing organs and tissues lost to injury and disease, face the obstacle of donor cell rejection by the host. Nuclear reprogramming can create iPS cells that are genetically identical to that of the donor, thus allowing a patient to be the donor for an iPS cell line that may serve as starting material for replacement tissue and organs which will not be rejected by the patient. A key component to increasing the efficiency of reprogramming is a more comprehensive understanding of pluripotency. This would help to define more extensive genetic networks and additional players that could be introduced or engineered to increase reprogramming efficiency.

Much of the information gained from studying pluripotency has been done so using genomic approaches; such as DNA microarrays or "chips"", and variations on chip experiments such as chIP-chip, chromatin immunoprecipitation followed by chip analysis, and more recently bio-chIP and bio-chIP-chip which is in vivo biotinylation mediated chIP coupled with target mapping (chip). The significant findings achieved using these approaches reflect the shifting landscape of how biological qustions are being asked-on a global rather than gene by gene level. Innovative and improved methods are enabling us to understand the extensive gene and protein networks involved in pluripotency which will, in turn, inform reprogramming approaches.

Recently, much attention has been focused on a small suite of transcription factors including the "reprogramming factors" (Oct4, Sox2, Klf4, and c-Myc) and others, such as Nanog, found to be required to maintain cells in a pluripotent state (Stadtfeld et al., 2008). In a recent paper by Stu Orkin's lab at the Harvard Stem Cell Institute and Dana Farber Cancer Center (Kim et al., 2008), they explored the molecular basis of these requirements using a powerful bio ChIP (in vivo-biotinylated chIP) and bio chIP-chIP approach, which gets around some of the limitations of many antibodies in traditional chIP experiments.

Orkin's group identified target promoters of nine of the reprogramming factors on a global scale in embryonic stem cells. They were able to examine their promoters and distinguish two classes of target genes based on the requirements to activate or repress them suggesting differential regulation of these targets related to the factors occupying the promoter. While other groups have used chip based approaches to probe the downstream targets of Oct4, Sox2,and Nanog in mouse and human embryonic stem cells, the studies by Orkin and colleagues expand the set analyzed to nine transcription factors, examined on a global scale and provide a background with which to ask more detailed questions about the reprogramming activities of these factors.

Another recent study, also taking a whole genome approach toward understanding the genetic networks involved in pluripotency, Bing Lim and colleagues were interested in defining the mechanism by which the Wnt pathway, ubiquitous in many developmental processes, plays a role in maintaining pluripotency. The researchers coupled chromatin immunpprecipitation and DNA chip analysis (ChIP-on-chip) in order to identify previously unknown targets of Tcf3, a downstream effector of the Wnt pathway known to be involved in pluripotency. Their experiments revealed that, along with a rang of other targets previously implicated in developmental processes, Tcf3. Interestingly, they found that Tcf3 binds and represses Oct4 one of the core reprogramming factors which affects Oct4 as well Nanog levels, another factor involved in pluripotency. The genomic approaches taken allowed researchers to examine multiple genes at once, revealing a complex genetic network that would not have so clearly emerged using a more piecemeal approach.

Whole genome studies have come into their own at an ideal time to serve as a tool to better our understanding of pluripotency, as well as differentiation. A greater knowledge of the two states will ultimately help us understand the means for more efficient and targeted flux between the two.

References

Kim, J., Chu, J., Shen, X., Wang, J., Orkin, S.H. (2008) An extended transcriptional network for pluripotency of embryonic stem cells. Cell 132, 1049-61.
Stadtfeld, M., Maherali, N., Breault, D.T., Hochedlinger, K. (2008) Defining molecular cornerstones during fibroblast to iPS cell reprogramming in mouse. Cell Stem Cell. 2, 230-40.
Tam, W.L., Lim, C.Y., Han, J., Zhang, J., Ang, Y.S., Ng, H.H., Yang H, Lim, B. (2008) Tcf3 Regulates Embryonic Stem Cell Pluripotency and Self-Renewal by the Transcriptional Control of Multiple Lineage Pathways. Stem Cells. May 8. [Epub ahead of print]

Spotlight Article

Dissecting direct reprogramming through integrative genomic analysis

This month's spotlighted article, published online in the journal Nature, is by new HSCI Principal Faculty member Alexander Meissner, PhD, Assistant Professor in Harvard's new inter-school Department of Stem Cell and Regenerative Biology and Associate Member of the Broad Institute.

Abstract:

Somatic cells can be reprogrammed to a pluripotent state through the ectopic expression of defined transcription factors. Understanding the mechanism and kinetics of this transformation may shed light on the nature of developmental potency and suggest strategies with improved efficiency or safety. Here we report an integrative genomic analysis of reprogramming of mouse fibroblasts and B lymphocytes. Lineage-committed cells show a complex response to the ectopic expression involving induction of genes downstream of individual reprogramming factors. Fully reprogrammed cells show gene expression and epigenetic states that are highly similar to embryonic stem cells. In contrast, stable partially reprogrammed cell lines show reactivation of a distinctive subset of stem-cell-related genes, incomplete repression of lineage-specifying transcription factors, and DNA hypermethylation at pluripotency-related loci. These observations suggest that some cells may become trapped in partially reprogrammed states owing to incomplete repression of transcription factors, and that DNA de-methylation is an inefficient step in the transition to pluripotency. We demonstrate that RNA inhibition of transcription factors can facilitate reprogramming, and that treatment with DNA methyltransferase inhibitors can improve the overall efficiency of the reprogramming process.

Mikkelsen TS, Hanna J, Zhang X, Ku M, Wernig M, Schorderet P, Bernstein BE, Jaenisch R, Lander ES, Meissner A. Dissecting direct reprogramming through integrative genomic analysis. Nature. 2008 May 28.

Review and Commentary Articles

Weissleder R, Pittet MJ. Imaging in the era of molecular oncology. Nature. 2008 Apr 3;452(7187):580-9. Review. Read Abstract.
Martin-Puig S, Wang Z, Chien KR. Lives of a heart cell: tracing the origins of cardiac progenitors. Cell Stem Cell. 2008 Apr 10;2(4):320-31. Read Abstract.
Wang Y, Armstrong SA. Cancer: inappropriate expression of stem cell programs? Cell Stem Cell. 2008 Apr 10;2(4):297-9. Read Abstract.
Koh I, Hong R, Weissleder R, Josephson L. Sensitive NMR Sensors Detect Antibodies to Influenza. Angew Chem Int Ed Eng. 2008 Apr 21;47(22):4119-4121. No abstract available. Read Abstract.
Punzo C, Cepko CL. Ultrasound-guided in utero injections allow studies of the development and function of the eye. Dev Dyn. 2008 Apr;237(4):1034-42. Read Abstract.
Papayannopoulou T, Scadden DT. Stem-cell ecology and stem cells in motion. Blood. 2008 Apr 15;111(8):3923-30. Read Abstract.
Williams DA. Foamy virus vectors come of age. Mol Ther. 2008 Apr;16(4):635-6. No abstract available. Read Abstract.

Blood

Min IM, Pietramaggiori G, Kim FS, Passegue E, Stevenson KE, Wagers AJ. The transcription factor EGR1 controls both the proliferation and localization of hematopoietic stem cells. Cell Stem Cell. 2008 Apr 10;2(4):380-91. Read Abstract.
Muller LU, Milsom MD, Kim MO, Schambach A, Schuesler T, Williams DA. Rapid Lentiviral Transduction Preserves the Engraftment Potential of Fanca(-/-) Hematopoietic Stem Cells. Mol Ther. 2008 Apr 8. Read Abstract.

Cancer

Kirstetter P, Schuster MB, Bereshchenko O, Moore S, Dvinge H, Kurz E, Theilgaard-Monch K, Mansson R, Pedersen TA, Pabst T, Schrock E, Porse BT, Jacobsen SE, Bertone P, Tenen DG, Nerlov C. Modeling of C/EBPalpha mutant acute myeloid leukemia reveals a common expression signature of committed myeloid leukemia-initiating cells. Cancer Cell. 2008 Apr;13(4):299-310. Read Abstract.
Wernig G, Kharas MG, Okabe R, Moore SA, Leeman DS, Cullen DE, Gozo M, McDowell EP, Levine RL, Doukas J, Mak CC, Noronha G, Martin M, Ko YD, Lee BH, Soll RM, Tefferi A, Hood JD, Gilliland DG. Efficacy of TG101348, a selective JAK2 inhibitor, in treatment of a murine model of JAK2V617F-induced polycythemia vera. Cancer Cell. 2008 Apr;13(4):311-20. Read Abstract.
Austin KM, Gupta ML, Coats SA, Tulpule A, Mostoslavsky G, Balazs AB, Mulligan RC, Daley G, Pellman D, Shimamura A. Mitotic spindle destabilization and genomic instability in Shwachman-Diamond syndrome. J Clin Invest. 2008 Apr;118(4):1511-8. Read Abstract.
Quintas-Cardama A, Tong W, Manshouri T, Vega F, Lennon PA, Cools J, Gilliland DG, Lee F, Cortes J, Kantarjian H, Garcia-Manero G. Activity of tyrosine kinase inhibitors against human NUP214-ABL1-positive T cell malignancies. Leukemia. 2008 Apr 10. Read Abstract.

Cell Biology

Saharinen P, Eklund L, Miettinen J, Wirkkala R, Anisimov A, Winderlich M, Nottebaum A, Vestweber D, Deutsch U, Koh GY, Olsen BR, Alitalo K. Angiopoietins assemble distinct Tie2 signalling complexes in endothelial cell-cell and cell-matrix contacts. Nat Cell Biol. 2008 May;10(5):527-37. Epub 2008 Apr 20. Read Abstract.

Developmental Biology

Wu X, Tu X, Joeng KS, Hilton MJ, Williams DA, Long F. Rac1 activation controls nuclear localization of beta-catenin during canonical Wnt signaling. Cell. 2008 Apr 18;133(2):340-53. Read Abstract.
Wang J, Levasseur DN, Orkin SH. Requirement of Nanog dimerization for stem cell self-renewal and pluripotency. Proc Natl Acad Sci USA. 2008 Apr 29;105(17):6326-31. Epub 2008 Apr 24. Read Abstract.
Sue N, Jack BH, Eaton SA, Pearson RC, Funnell AP, Turner J, Czolij R, Denyer G, Bao S, Molero-Navajas JC, Perkins A, Fujiwara Y, Orkin SH, Bell-Anderson K, Crossley M. Targeted disruption of the Basic Kruppel-like Factor (Klf3) gene reveals a role in adipogenesis. Mol Cell Biol. 2008 Apr 7. Read Abstract.
Kim DS, Ross SE, Trimarchi JM, Aach J, Greenberg ME, Cepko CL. Identification of molecular markers of bipolar cells in the murine retina. J Comp Neurol. 2008 Apr 10;507(5):1795-810. Read Abstract.

Diabetes

Cha HC, Oak NR, Kang S, Tran TA, Kobayashi S, Chiang SH, Tenen DG, Macdougald OA. Phosphorylation of C/EBPalpha regulates GLUT4 expression and glucose transport in adipocytes. J Biol Chem. 2008 Apr 11. Read Abstract.

Imaging

Shah K, Hingtgen S, Kasmieh R, Figueiredo JL, Garcia-Garcia E, Martinez-Serrano A, Breakefield X, Weissleder R. Bimodal viral vectors and in vivo imaging reveal the fate of human neural stem cells in experimental glioma model. J Neurosci. 2008 Apr 23;28(17):4406-13. Read Abstract.
Kelly KA, Bardeesy N, Anbazhagan R, Gurumurthy S, Berger J, Alencar H, Depinho RA, Mahmood U, Weissleder R. Targeted nanoparticles for imaging incipient pancreatic ductal adenocarcinoma. PLoS Med. 2008 Apr 15;5(4):e85. Read Abstract.
Kelly KA, Setlur SR, Ross R, Anbazhagan R, Waterman P, Rubin MA, Weissleder R. Detection of early prostate cancer using a hepsin-targeted imaging agent. Cancer Res. 2008 Apr 1;68(7):2286-91. Read Abstract.

Muscular System

Luth ES, Jun SJ, Wessen MK, Liadaki K, Gussoni E, Kunkel LM. Bone marrow side population cells are enriched for progenitors capable of myogenic differentiation. J Cell Sci. 2008 May 1;121(Pt 9):1426-34. Epub 2008 Apr 8. Read Abstract.

Nervous System

Wang X, Liu J, Zhu H, Tejima E, Tsuji K, Murata Y, Atochin DN, Huang PL, Zhang C, Lo EH. Effects of Neuroglobin Overexpression on Acute Brain Injury and Long-Term Outcomes After Focal Cerebral Ischemia. Stroke. 2008 Apr 10. Read Abstract.
Kohno T, Wang H, Amaya F, Brenner GJ, Cheng JK, Ji RR, Woolf CJ. Bradykinin enhances AMPA and NMDA receptor activity in spinal cord dorsal horn neurons by activating multiple kinases to produce pain hypersensitivity. J Neurosci. 2008 Apr 23;28(17):4533-40. Read Abstract.
Lagali PS, Balya D, Awatramani GB, Munch TA, Kim DS, Busskamp V, Cepko CL, Roska B. Light-activated channels targeted to ON bipolar cells restore visual function in retinal degeneration. Nat Neurosci. 2008 Apr 27. Read Abstract.
Hedlund EM, Pruszak J, Lardaro T, Ludwig W, Viñuela A, Kim KS, Isacson O. Embryonic Stem (ES) Cell-derived Pitx3-eGFP Midbrain Dopamine Neurons Survive Enrichment by FACS and Function in an Animal Model of Parkinson's Disease. Stem Cells. 2008 Apr 3. Read Abstract.
Wernig M, Zhao JP, Pruszak J, Hedlund E, Fu D, Soldner F, Broccoli V, Constantine-Paton M, Isacson O, Jaenisch R. Neurons derived from reprogrammed fibroblasts functionally integrate into the fetal brain and improve symptoms of rats with Parkinson's disease. Proc Natl Acad Sci USA. 2008 Apr 15;105(15):5856-61. Epub 2008 Apr 7. Read Abstract.
Mendez I, Vinuela A, Astradsson A, Mukhida K, Hallett P, Robertson H, Tierney T, Holness R, Dagher A, Trojanowski JQ, Isacson O. Dopamine neurons implanted into people with Parkinson's disease survive without pathology for 14 years. Nat Med. 2008 May;14(5):507-9. Epub 2008 Apr 6. Read Abstract.

Renal System

Zhang J, Brown RP, Shaw M, Vaidya VS, Zhou Y, Espandiari P, Sadrieh N, Stratmeyer M, Keenan J, Kilty CG, Bonventre JV, Goering PL. Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidney of Gentamicin-, Mercury-, or Chromium-Treated Rats: Relationship to Renal Distributions of iNOS and Nitrotyrosine. Toxicol Pathol. 2008 Apr 25. Read Abstract.

Tissue Engineering

Rocha FG, Sundback CA, Krebs NJ, Leach JK, Mooney DJ, Ashley SW, Vacanti JP, Whang EE. The effect of sustained delivery of vascular endothelial growth factor on angiogenesis in tissue-engineered intestine. Biomaterials. 2008 Jul;29(19):2884-90. Epub 2008 Apr 8. Read Abstract.

The Harvard Stem Cell Institute is a scientific collaborative established to fulfill the promise of stem cell biology as the basis for cures and treatments for a wide range of chronic medical conditions.

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