TMA endorses funding for stem cell research

AUSTIN - The largest doctors group in President Bush's home state has endorsed embryonic stem cell research and says federal funding should be restored for new studies to combat disease.

The Texas Medical Association, the country's largest state physician organization with more than 39,000 members, recently adopted a resolution supporting embryonic and adult stem cell research and a process called "therapeutic cloning," but said it would oppose cloning to produce a human child. The endorsement was publicized in the TMA's monthly magazine released Wednesday.

Federal help for embryonic stem cell research has been limited since 2001, when Bush signed an executive order preventing its expansion. Because the extraction of stem cells destroys day-old embryos, the process is opposed by groups who link it to abortion.

"There's a very strong belief these stem cells can offer the world of medicine a strategy for fighting chronically debilitating diseases," said Dr. Leonides Cigarroa, a family physician from Laredo who chairs the TMA's council on scientific affairs. "The belief is this can improve quality of life."

Stem cells are the body's building blocks. Scientists believe they can be coaxed to develop into specific cell types that can be used to replace damaged tissue and treat such conditions as diabetes, Parkinson's disease and spinal cord injuries.

Advocates of embryonic stem cell research argue that it could help scientists cure diseases. The debate over its funding gained new energy with the death of former President Ronald Reagan after a decade-long battle with Alzheimer's.

Shortly before Reagan's June 5 death, Sen. John Kerry of Massachusetts, the presumptive Democratic nominee for president, and 57 other senators asked Bush to relax the restrictions. The White House declined.

Cigarroa said the TMA resolution was adopted in May and was not done for political reasons.

But he said he hopes TMA's position will help win more federal funding for stem cell research.

"We try not to address politics at all," he said. "We're addressing science .... This is a hot topic. There is a lot of passion."

Dr. Beverly Nuckols, a family physician from New Braunfels, argued against it in May. She said many doctors support her position that embryonic stem cell research and therapeutic cloning are morally wrong.

Nuckols is on the board of directors for the Texas Physicians Resource Council, a separate group from the TMA that she said has about 400 members.

Organized to support the "Judeo-Christian family through involvement in medical issues," the council's Web site says it would support a legal ban on all embryonic and cloning research.

"I don't see how you can separate ethics from science," Nuckols said. "It's the destruction of human embryos. It's a matter of human rights."

Nuckols said research on adult stem cells, umbilical cord blood cells, bone marrow and other areas are acceptable alternatives.

While most embryonic stem cells are taken from excess embryos created through test-tube fertilization and donated by fertility clinics, many scientists believe they will have to be taken from embryos cloned with the patient's own DNA to avoid immune-system rejection problems.

The TMA resolution supports funding for somatic cell nuclear transfer technology, or "therapeutic cloning." In that process, the nucleus would be removed from a donor egg and replaced with the nucleus from a donor cell to help create stem cells, Cigarroa said.

He said the therapeutic cloning process will be necessary as federally funded stem cell projects projects is gradually reduced and not replaced.

Nuckols dismisses therapeutic cloning as human cloning with a fancy name, calling it unethical. Cigarroa said TMA's resolution opposes cloning to produce a human child.

"None of us supports cloning a human being," Cigarroa said. "We want to help people come up with answers to diseases."

There's hope for adult pancreatic stem cells in the near future:

Invited rapid communication
Pluripotency of adult stem cells derived from human and rat pancreas

C. Kruse1 , M. Birth2, J. Rohwedel3, K. Assmuth3, A. Goepel3 and T. Wedel4
(1) Fraunhofer-Institute of Biomedical Engineering, Group of Cell Differentiation and Cell Technology, University of Lübeck, MFC Innovationscampus 1, Maria-Goeppert-Str. 1, 23538 Lübeck, Germany
(2) Department of Surgery, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
(3) Department of Medical Molecular Biology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany
(4) Department of Anatomy, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany

Received: 2 April 2004 Accepted: 3 April 2004 Published online: 26 May 2004
Abstract Adult stem cells are undifferentiated cells found within fully developed tissues or organs of an adult individuum. Until recently, these cells have been considered to bear less self-renewal ability and differentiation potency compared to embryonic stem cells. In recent studies an undifferentiated cell type was found in primary cultures of isolated acini from exocrine pancreas termed pancreatic stellate cells. Here we show that pancreatic stellate-like cells have the capacity of extended self-renewal and are able to differentiate spontaneously into cell types of all three germ layers expressing markers for smooth muscle cells, neurons, glial cells, epithelial cells, chondrocytes and secretory cells (insulin, amylase). Differentiation and subsequent formation of three-dimensional cellular aggregates (organoid bodies) were induced by merely culturing pancreatic stellate-like cells in hanging drops. These cells were developed into stable, long-term, in vitro cultures of both primary undifferentiated cell lines as well as organoid cultures. Thus, evidence is given that cell lineages of endodermal, mesodermal, and ectodermal origin arise spontaneously from a single adult undifferentiated cell type. Based on the present findings it is assumed that pancreatic stellate-like cells are a new class of lineage uncommitted pluripotent adult stem cells with a remarkable self-renewal ability and differentiation potency. The data emphasize the versatility of adult stem cells and may lead to a reappraisal of their use for the treatment of inherited disorders or acquired degenerative diseases.
PACS 87.17.-d; 87.18.Ed; 81.17.Ez; 87.18.-h

and more,

http://gut.bmjjournals.com/cgi/content/full/51/4/574

For now, take a look at this, from Australia:

http://news.ninemsn.com.au/article.aspx?id=11509

New lab offers cell-based cures
Wednesday, June 30, 2004

By Sheryl Taylor

A new world-class laboratory, Sydney Cellular Therapies Laboratory, has cured a handful of people with type 1 diabetes. The breakthrough was made possible by special technology to process human cells and is set to develop other cures for cancers and other conditions affecting thousands of Australians.

Barbara Dunn and Julie Mudd are two of the first six Australians to receive life-saving cell transplants from this laboratory for their type 1diabetes after their bodies had stopped making insulin which regulates glucose in the body. But it became a sudden, almost deadly, event when it happened to Julie while she was employed an aid worker nine years ago.

"Over a couple of weeks I became desperately ill and was told I only had 24 hours to live," she said.

A mercy dash to intensive care back in Australia saved her but like Barbara has been dependent on daily insulin. Now, after two procedures to transplant replacement insulin-making cells, Barbara is cured. Following Barbara's success, Julie expects the same result in a week. Then they'll both need anti-rejection drugs which they both claim is a small trade-off compared to lifelong risks of diabetic complications.

"I don't look at my daughter any more wondering if I'm going to see her start school," said Julie. "I can look at her now and think I'm going to be there to watch her grow up."

The $600,000 Sydney Cellular Therapies Laboratory is the state's first specialist lab for processing blood and bone marrow stem cells, and pancreatic islet cells. It transforms 10 years of research into new, cell-based treatments for patients with cancer, blood diseases and diabetes.

"This is a very big breakthrough. Using a cell-based therapy to treat a chronic disease is very new and it's the way of the future," said Professor Phillip O'Connell, Sydney Cell Therapies Lab. Moving forward, the lab at Westmead Hospital will expand on the diabetes treatment previously considered experimental and only available in Europe and the US.

Professor Ken Bradstock, Head of Bone Marrow Transplant (BMT) at Westmead Hospital, said the new lab was "a step into the future" and means patients suffering from blood cancers, such as leukaemia, can now be offered new developmental treatments.

And, here's the reason that there's so little reporting on the breakthroughs in adult stem cell research:
http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v429/n6992/full/429590b_fs.html

"""Others say the paper's high profile will strengthen opposition to embryonic stem-cell research. "I am concerned that the whole field might suffer if news about alleged breakthroughs is spread in this way," says Oliver Brüstle, head of reconstructive neurobiology at the University of Bonn."""

(Nature requires a subscription to read the articles)

Nature 429, 590 (10 June 2004); doi:10.1038/429590b

Critics blast 'premature' paper on adult stem cells

QUIRIN SCHIERMEIER AND MARTIN LEEB

[MUNICH] A stem-cell paper published last month in an online physics journal has created quite a stir. The paper, which was described as a "breakthrough" in adult stem-cell technology at a public announcement in Germany, is scientifically premature, experts say, and may lead to a surge in protests against research using embryonic lines.

In the current issue of Applied Physics A (doi:10.1007/s00339-004-2816-6; 2004) — an online journal published by Springer that normally reports materials-science research — a team of German biologists describes a technique for isolating stem cells from the pancreas of adult humans and rats. In culture, the cells differentiated into multiple cell lineages, such as brain and muscle cells, the team reports. If confirmed, the discovery would allow researchers often to use stem cells from adults instead of from embryos — a particularly controversial source in Germany.

At a press conference in Berlin on 28 May, politicians of the Christian Democrats and Social Democrats referred to the study as "groundbreaking". Wolfgang Wodarg, health spokesman for the Social Democrats, said it was a blow to supporters of research involving human embryonic stem cells.

But leading stem-cell researchers rebuked the team and its host institutions — the University of Lübeck and the Fraunhofer Institute for Biomedical Engineering (IBMT) in St Ingbert — for publishing premature results. They point out that the paper was accepted one day after it was submitted, without full peer review. The paper provides little evidence for many of its claims, says Hans Schöler, a stem-cell researcher at the University of Pennsylvania in Philadelphia.

Michael Stuke, editor-in-chief of Applied Physics A, says he took the advice of several experts before deciding to publish. "If I think that a topic is really hot and needs to be disseminated without the delay typical for major journals, I won't hesitate to invite biologists to publish in our journal," he says.

Publishing the data in an unreviewed physics journal was a "less-than-ideal solution", admits Günter Fuhr, director of the IBMT, who supervised the study. But he backs their decision to inform the public of their results at an early stage. Requests from Nature to interview the lead author of the paper, Charli Kruse of the University of Lübeck, were deferred to Fuhr.

Others say the paper's high profile will strengthen opposition to embryonic stem-cell research. "I am concerned that the whole field might suffer if news about alleged breakthroughs is spread in this way," says Oliver Brüstle, head of reconstructive neurobiology at the University of Bonn.""""

On the other hand, stem cells may not be useful, no matter what the origin (from the same issue of Nature,

http://www.nature.com/cgi-taf/DynaPage.taf?file=/nature/journal/v429/n6987/abs/nature02520_fs.html
""""
We conclude that pre-existing -cells are the major source for new -cells during adult life, as well as during regeneration from partial pancreatectomy (Fig. 1a, model 3). This conclusion challenges the view that adult stem cells (undifferentiated cells capable of self-renewal and differentiation) are significant in -cell homeostasis. Instead, we submit that terminally differentiated -cells retain a proliferative capacity that can account for turnover and expansion throughout a mouse's life.

There are several ways in which our data could be reconciled with previous reports claiming the existence of pancreatic stem cells. First, our experiments cannot prove the absence of stem cells, given the degree of variation in labelling efficiency inherent to the CreER system. It is possible that rare stem or progenitor cells exist but give rise to a small, physiologically unimportant fraction of[beta] -cells17. A convincing demonstration of such putative stem cells could be provided by genetic lineage tracing, for example by using a duct cell promoter driving Cre recombinase. Second, it is formally possible that the insulin gene is transcriptionally active in stem cells. If so, these putative stem cells must be unipotent because HPAP+ cells gave rise only to [beta]-cells. Even after a long chase, no other endocrine, exocrine or ductal cells were HPAP+. In effect, such putative unipotent stem cells would be indistinguishable from [beta]-cells. Third, facultative pancreatic stem cells might exist and be activated in response to specific insults other than pancreatectomy24, 30. Fourth, the vast majority of Px and regeneration studies were done with rats rather than mice and it is possible that these species differ in the mode of regeneration. Last,[beta] -cells could transiently dedifferentiate (and possibly acquire stem cell markers) before generating new [beta]-cells12. A similar process is thought to occur during angiogenesis, in which differentiated endothelial cells give rise to 'activated endothelium', which then proliferates and organizes into new blood vessels31. However, there is currently no evidence for such a mechanism in the pancreas.

It has been suggested that new lobes, including new islets, are constantly generated in the adult pancreas13, 32. In contrast, the data presented here support the idea that the number of islets during adult life is fixed, with homeostatic responses (for example, -cell expansion) being performed by differentiated cells residing in these structural units. Indeed, it was recently reported that average islet size, but not islet density, increases with age33-35. Our studies indicate that there is a time during embryonic development, or early postnatal life, at which the number of islets is set. The data also indicate that -cell formation from undifferentiated precursors ceases at this time in that new (beta)-cells that form subsequently come from pre-existing (beta)-cells. Further experiments are required to determine when this switch occurs.

Our results emphasize the importance of using direct lineage tracing, rather than histological snapshots, to determine a cell of origin or the provenance of a given tissue. The method presented here can be adapted to assess the contribution of stem cells in other organs during growth, normal turnover and regeneration. In addition, it could be used to determine the cell of origin in cancer models.

One implication of this study concerns possible cell-based therapies for type I diabetes, in which (beta)-cells are destroyed by an autoimmune attack. It points to the significant proliferative potential of differentiated (beta)-cells in vivo, a capacity that might be exploited for expansion to a clinically useful mass. In addition, the results highlight the fact that embryonic stem cells are currently the only type of stem cell that is unquestionably capable of differentiation into -cells.

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