David Kirkpatrick

July 3, 2009

Stem cell news — differences and ethics

Two releases from yesterday on stem cells. Number one is on the found differences between reprogrammed skin cells and embryonic stem cells. Second is a call for stem cell debates by bioethicists before the science gets too far ahead of ethical considerations.

The first release:

UCLA scientists find molecular differences between embryonic stem cells and reprogrammed skin cells

UCLA researchers have found that embryonic stem cells and skin cells reprogrammed into embryonic-like cells have inherent molecular differences, demonstrating for the first time that the two cell types are clearly distinguishable from one another.

The data from the study suggest that embryonic stem cells and the reprogrammed cells, known as induced pluripotent stem (iPS) cells, have overlapping but still distinct gene expression signatures. The differing signatures were evident regardless of where the cell lines were generated, the methods by which they were derived or the species from which they were isolated, said Bill Lowry, a researcher with the Broad Stem Cell Research Center and a study author.

“We need to keep in mind that iPS cells are not perfectly similar to embryonic stem cells,” said Lowry, an assistant professor of molecular, cell and developmental biology. “We’re not sure what this means with regard to the biology of pluripotent stem cells. At this point our analyses comprise just an observation. It could be biologically irrelevant, or it could be manifested as an advantage or a disadvantage.”

The study appears in the July 2, 2009 issue of the journal Cell Stem Cell.

The iPS cells, like embryonic stem cells, have the potential to become all of the tissues in the body. However, iPS cells don’t require the destruction of an embryo.

The study was a collaboration between the labs of Lowry and UCLA researcher Kathrin Plath, who were among the first scientists and the first in California to reprogram human skin cells into iPS cells. The researchers performed microarray gene expression profiles on embryonic stem cells and iPS cells to measure the expression of thousands of genes at once, creating a global picture of cellular function.

Lowry and Plath noted that, when the molecular signatures were compared, it was clear that certain genes were expressed differently in embryonic stem cells than they were in iPS cells. They then compared their data to that stored on a National Institutes of Health data base, submitted by laboratories worldwide. They analyzed that data to see if the genetic profiling conducted in other labs validated their findings, and again they found overlapping but distinct differences in gene expression, Lowry said.

“This suggested to us that there could be something biologically relevant causing the distinct differences to arise in multiple labs in different experiments,” Lowry said. “That answered our first question: Would the same observation be made with cell lines created and maintained in other laboratories?”

Next, UCLA researchers wanted to confirm their findings in iPS cell lines created using the latest derivation methods. The cells from the UCLA labs were derived using an older method that used integrative viruses to insert four genes into the genome of the skin cells, including some genes known to cause cancer. They analyzed cell lines derived with newer methods that do not require integration of the reprogramming factors. Their analysis again showed different molecular signatures between iPS cells and their embryo-derived counterparts, and these signatures showed a significant degree of overlap with those generated with integrative methods.

To determine if this was a phenomenon limited to human embryonic stem cells, Lowry and Plath analyzed mouse embryonic stem cells and iPS lines derived from mouse skin cells and again validated their findings. They also analyzed iPS cell lines made from mouse blood cells with the same result

“We can’t explain this, but it appears something is different about iPS cells and embryonic stem cells,” Lowry said. “And the differences are there, no matter whose lab the cells come from, whether they’re human or mouse cells or the method used to derive the iPS cells. Perhaps most importantly, many of these differences are shared amongst lines made in various ways.”

Going forward, UCLA researchers will conduct more sophisticated analyses on the genes being expressed differently in the two cell types and try to understand what is causing that differential expression. They also plan to differentiate the iPS cells into various lineages to determine if the molecular signature is carried through to the mature cells. In their current study, Lowry and Plath did not look at differentiated cells, only the iPS and embryonic stem cells themselves.

Further study is crucial, said Mark Chin, a postdoctoral fellow and first author of the study.

“It will be important to further examine these cells lines in a careful and systematic manner, as has been done with other stem cell lines, if we are to understand the role they can play in clinical therapies and what effect the observed differences have on these cells,” he said.

 

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The stem cell center was launched in 2005 with a UCLA commitment of $20 million over five years. A $20 million gift from the Eli and Edythe Broad Foundation in 2007 resulted in the renaming of the center. With more than 150 members, the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research is committed to a multi-disciplinary, integrated collaboration of scientific, academic and medical disciplines for the purpose of understanding adult and human embryonic stem cells. The center supports innovation, excellence and the highest ethical standards focused on stem cell research with the intent of facilitating basic scientific inquiry directed towards future clinical applications to treat disease. The center is a collaboration of the David Geffen School of Medicine, UCLA’s Jonsson Cancer Center, the Henry Samueli School of Engineering and Applied Science and the UCLA College of Letters and Science. To learn more about the center, visit our web site at http://www.stemcell.ucla.edu.

Head below the fold for the second release on a call for an ethics debate on stem cells. (more…)

March 19, 2009

Stem cell differentiation breakthrough

Looks like this research is helping to uncover the building blocks of stem cells and should lead to even bigger breakthroughs.

The release:

Protein is Key to Embryonic Stem Cell Differentiation

 

Burnham Scientists Identify Protein that Controls Differentiation in Human and Mouse Embryonic Stem Cells

 
LA JOLLA, Calif., March 18, 2009 — Investigators at Burnham Institute for Medical Research (Burnham) have learned that a protein called Shp2 plays a critical role in the pathways that control decisions for differentiation or self-renewal in both human embryonic stem cells (hESCs) and mouse embryonic stem cells (mESCs).

The research, led by Gen-Sheng Feng, Ph.D., differs with some earlier findings that suggested hESCs and mESCs differentiate as a result of different signaling mechanisms. The discovery that Shp2 has a conserved role between mice and humans suggests an interesting common signaling mechanism between mESCs and hESCs, despite the known distinct signaling paths and biological properties between the two types of pluripotent stem cells. The study was published online in the journal PLoS ONE on March 17, 2009.

Embryonic stem cells (ESCs) are pluripotent cells that can differentiate to become more than 200 different cell types. Because of their plasticity, ESCs have been suggested as potential therapies for numerous diseases and conditions, including neurodegenerative diseases, spinal cord injury and tissue damage. Development of such therapies is largely dependent on fully understanding and controlling the processes that lead to differentiation of hESCs into specialized cell types.

“There are many signaling pathways that help embryonic stem cells decide their fate,” said Dr. Feng. “We found that the Shp2 protein acts as a coordinator that fine-tunes the signal strength of multiple pathways and gives us a better understanding of the fundamental signaling methods that determine whether a stem cell’s fate will be self-renewal or differentiation.”

In the study, the Feng lab created mutant Shp2 mESCs and showed that differentiation was dramatically impaired as the cells self-renewed as stem cells. The researchers also demonstrated small interfering RNAs in hESCs reduce Shp2 expression and subsequent cell differentiation. Feng and colleagues screened chemical libraries and identified a small-molecule inhibitor of Shp2 that, in small doses, partially inhibits differentiation in both mESCs and hESCs. Taken together, these results suggest a conserved role for Shp2 in ESC differentiation and self-renewal in both mice and humans.

“This opens the door for new experimental reagents that will amplify the self-renewal process to create more stem cells for research and potential clinical use in the future,” Dr. Feng added. “This research also suggests that comparative analysis of mouse and human embryonic stem cells will provide fundamental insight into the cellular processes that determine ‘stemness,’ a critical question that remains to be answered in the stem cell biology field.”

About Burnham Institute for Medical Research
Burnham Institute for Medical Research is dedicated to revealing the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. Burnham, with operations in California and Florida, is one of the fastest-growing research institutes in the country. The Institute ranks among the top-four institutions nationally for NIH grant funding and among the top 25 organizations worldwide for its research impact. Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, infectious and inflammatory and childhood diseases. The Institute is known for its world-class capabilities in stem cell research and drug discovery technologies. Burnham is a nonprofit, public benefit corporation.

September 7, 2008

Latest DC BS on stem cells

The entire issue around stem cell research just makes me mad. It’s ridiculous that a country like the United States allows Dark Age ideals and intelligence to influence science. This year’s GOP platform includes a call for a ban on any form of stem cell research public or private.

At any rate, here’s the release:

Updated guidelines for stem cell research released

WASHINGTON — The National Academies today released amended guidelines for research involving human embryonic stem cells, revising those that were issued in 2005 and updated in 2007. The Academies originally produced the guidelines to offer a common set of ethical standards for the responsible conduct of research using human stem cells, an area that, due to an absence of comprehensive federal funding, was lacking national standards. Since their initial release, the guidelines have served effectively as the basis for oversight of this research in the United States. In addition, a standing advisory committee — a joint project between the Academies’ National Research Council and Institute of Medicine — was established to monitor and review scientific advances and determine any need for revisions.

Embryonic stem cells have the potential to produce all of the body’s cell types. Researchers are working to harness stem cells’ ability both to regenerate themselves and produce specialized cells that may lead to medical treatments that replace certain types of cells damaged or lost to debilitating illness and injury, such as nerve cells.

One reason for the 2008 modifications is to provide guidance on the derivation and use of new human stem cells that were first developed last year. These cells — called “induced pluripotent cells” — are made by reprogramming nonembryonic adult cells into a stem-cell-like state, in which they can be manipulated to form a wide array of specialized body cells. Although induced pluripotent stem cells can be derived without using embryos, the ethical and policy concerns related to their potential uses are similar to those pertaining to human embryonic stem cells. For example, issues arising from mixing human and animal cells in a single organism are relevant for stem cells from both embryonic and nonembryonic sources. However, derivation of induced pluripotent stem cells does not require special stem cell expertise and is adequately covered by current Institutional Review Board regulations, the report says.

At this time it is still undetermined which stem cell types will prove the most useful for regenerative medicine, as most likely each will have some utility, noted the committee that wrote the report. Therefore, the need for research with human embryonic stem cells still exists despite the availability of new cell sources.

The amended guidelines also clarify that “direct expenses” for reimbursement to women donating their eggs for use in stem cell research may include costs associated with travel, housing, child care, medical care, health insurance, and actual lost wages. This language extends the 2005 guidelines, which stated that women who undergo hormonal induction to generate eggs specifically for research purposes should be reimbursed only for “direct expenses” incurred as a result of the procedure, although they did not specify which expenses qualified as direct. The committee stressed that reimbursement for lost wages is not a payment for eggs; the intent is to leave all donors neither better off nor worse off financially.

To instill a high level of confidence that institutions and their researchers are conducting stem cell research responsibly, the guidelines recommend that the public be informed about the types of stem cell research under way and how the research conforms to the institution’s established procedures. Moreover, the committee strongly suggested as a good management practice that institutions conducting human embryonic stem cell research carry out periodic audits of their embryonic stem cell research oversight (ESCRO) committees to ensure proper performance and make the findings of the audits available to the public. The audits should document decisions regarding the acceptance of research proposals and verify that cell lines in use were acceptably derived.

Additionally, the new guidelines clarify that an institutional ESCRO committee may conduct expedited review for research done exclusively in a laboratory dish or test tube that does not create new lines of stem cells but uses previously derived human embryonic stem cell lines. The original guidelines stated that research is “permissible after currently mandated review and proper notification of the relevant research institution.” However the word “notification” led some experts to question if the requirement could be fulfilled by merely informing ESCRO committees that the research would occur. Although allowing for expedited review, the guidelines still require an ESCRO committee to determine if the human embryonic stem cells have been acceptably derived.

Future committee deliberations will consider items for which additional information-gathering and more extensive debate and discussion may be necessary. For example, the National Institutes of Health determined that the human embryonic stem cell lines declared in 2001 by President George W. Bush to be eligible for federally funded research were derived from embryos donated with informed consent and without financial inducement. Based on this determination, the Academies’ 2007 guidelines had deemed those lines to have been acceptably derived. However, questions about their derivation were raised when this report was near completion. In addition, a breakthrough in the ability to “reprogram” adult cells from one type to another in a living animal was recently announced. The committee will continue to monitor developments in stem cell research to decide whether any future changes to the guidelines are warranted.

 

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The report was sponsored by the Ellison Medical Foundation, the Greenwall Foundation, and the Howard Hughes Medical Institute. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are private, nonprofit institutions that provide science, technology, and health policy advice under a congressional charter. The Research Council is the principal operating agency of the National Academy of Sciences and the National Academy of Engineering. A committee roster follows.

Copies of 2008 AMENDMENTS TO THE NATIONAL ACADEMIES’ GUIDELINES FOR HUMAN EMBRYONIC STEM CELL RESEARCH are available from the National Academies Press; tel. 202-334-3313 or 1-800-624-6242 or on the Internet at HTTP://WWW.NAP.EDU. Reporters may obtain a copy from the Office of News and Public Information (contacts listed above).

[This news release and report are available at HTTP://NATIONAL-ACADEMIES.ORG ]

NATIONAL RESEARCH COUNCIL

Division on Earth and Life Studies

Board on Life Sciences

and

INSTITUTE OF MEDICINE

Board on Health Sciences Policy

HUMAN EMBRYONIC STEM CELL RESEARCH ADVISORY COMMITTEE

R. ALTA CHARO, J.D.1 (CO-CHAIR)
Warren P. Knowles Professor of Law and Bioethics
Law School and School of Medicine and Public Health
University of Wisconsin
Madison

RICHARD O. HYNES, PH.D.1, 2 (CO-CHAIR)
Investigator
Howard Hughes Medical Institute; and
Daniel K. Ludwig Professor of Cancer Research
Koch Institute for Integrative Cancer Research and Department of Biology
Massachusetts Institute of Technology
Cambridge

ELI Y. ADASHI, M.D., M.S., FACOG1
Professor of Medical Science,
Former Dean of Medicine and Biological Sciences, and Frank L. Day Professor of Biology
Warren Alpert Medical School
Brown University
Providence, R.I.

BRIGID L.M. HOGAN, PH.D.1, 2
George Barth Geller Professor and Chair
Department of Cell Biology
Duke University Medical Center
Durham, N.C.

MARCIA IMBRESCIA
Trustee
Arthritis Foundation; and
Owner
Peartree Design
Lynnfield, Mass.

TERRY MAGNUSON, PH.D.
Sarah Graham Kenan Professor and Chair
Department of Genetics; and
Director
Carolina Center for Genome Sciences
University of North Carolina
Chapel Hill

LINDA B. MILLER, O.T.R., M.S.1
President
Volunteer Trustees Foundation
Washington, D.C.

JONATHAN D. MORENO, PH.D.1
Senior Fellow
Center for American Progress; and
David and Lyn Silfen University Professor and Professor of Medical Ethics and of the History and Sociology of Science
Center for Bioethics
University of Pennsylvania
Philadelphia

PILAR NICOLE OSSORIO, PH.D., J.D.
Associate Professor of Law and Bioethics
Law School
University of Wisconsin
Madison

E. ALBERT REECE, M.D., PH.D., M.B.A.1
Vice President for Medical Affairs, and Dean
School of Medicine
University of Maryland
Baltimore

JOSHUA R. SANES, PH.D.2
Professor
Department of Molecular and Cellular Biology, and
Paul J. Finnegan Family Director
Center for Brain Science
Harvard University
Cambridge, Mass.

HAROLD T. SHAPIRO, PH.D.1
President Emeritus, and
Professor of Economics and Public Affairs
Woodrow Wilson School of Public and International Affairs
Princeton University
Princeton, N.J.

JOHN E. WAGNER JR., M.D.
Professor of Pediatrics, and
Scientific Director of Clinical Research
Stem Cell Institute
University of Minnesota Medical School
Minneapolis

STAFF

ADAM P. FAGEN, PH.D.
Study Co-Director, Board on Life Sciences

BRUCE M. ALTEVOGT, PH.D.
Study Co-Director, Institute of Medicine

FRANCES E. SHARPLES, PH.D.
Director, Board on Life Sciences

1 Member, Institute of Medicine
2 Member, National Academy of Sciences

March 5, 2008

Lots of cool science and tech …

… from today’s KurzweilAI.net newsletter. The first two are bits about solar energy — the first on even “greener” solar panels, and the second on inkjet printing organic solar cells.

The third story is on cancer and embryonic stem cells. I look forward to the day the US government no longer bans federal funding of this research. I’m all for private research, but the fact is medical research in the US is pretty much handled through the NIH.

Here’s all three:

Greener Green Energy: Today’s solar cells give more than they take
Science News, March 1, 2008Solar power produces, per unit of energy, only about one-tenth as much carbondioxide and other harmful emissions (during manufacturing) as does conventional power generation, a new study by Brookhaven National Laboratory scientists shows.

These improvements in efficiency mean that today’s solar panels can “pay back” in only 1 to 3 years the energy needed to make them, the study concludes.

Improvements in manufacturing efficiency could reduce emissions from solar power by another 50 percent within 5 to 7 years, the researchers say.
Read Original Article>>

Konarka Announces First-Ever Demonstration of Inkjet Printed Solar Cells
nanowerk, Mar. 3, 2008Konarka Technologies has announced the company conducted the first-ever demonstration of manufacturing organic solar cells by efficient inkjet printing.

Read Original Article>>

Cancers inhibited by embryonic stem cell protein
NewScientist.com news service, March 4, 2008Northwestern University researchers have discovered that a protein, Lefty, produced by human embryonic stem cells (hESCs) can inhibit the growth and spread of breast cancer and malignant melanoma.

Similarities between stem cells and tumors–both are self-renewing and have the capacity to give rise to different cells types–previously led the researchers to find the protein Nodal, which facilitates cell growth, and suggested that stem cells must have a way to control Nodal.

The Northwestern researchers found that was Lefty. When aggressive tumor cells were exposed to the chemical environment of hESCs, which contained Lefty, their Nodal production fell sharply, and the tumor cells became less invasive and even started to die.
Read Original Article>>

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