Fwd: [TMIC] FYI - Two Stem Cell Advances

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June 21, 2002

Scientists Make Two Stem Cell Advances

By NICHOLAS WADE

wo significant advances in cell therapy, the notion of treating diseases with human cells instead of drugs, have been made by scientists at the National Institutes of Health and the University of Minnesota.

One advance shows how embryonic stem cells can be converted into copious quantities of the exact type of brain cell that is lost in Parkinson's disease, a technique that might have possible use in therapy.

The other research reports that cells surprisingly similar to embryonic stem cells can be isolated from people's bone marrow.

The two studies intertwine science with politics because they bear on whether embryonic stem cells, the primordial cells from which all body tissues develop, are necessary for realizing the dreams of cell therapy. The cells are obtained from early embryos discarded by fertility clinics. Opponents of abortion say destroying the frozen embryos, even if no woman wishes to bring them to term, is unethical.

The critics argue that any medical benefits of cell therapy can be obtained just as well with adult stem cells, which replenish tissues of the adult body. Scientists respond that embryonic stem cells offer many advantages that adult stem cells do not and that research on both types is needed at least until the promise of cell therapy is better understood. President Bush temporarily resolved the issue by ruling in August 2001 that government-financed researchers could work with the handful of human embryonic stem cell cultures already created, but not with any new ones.

The two new studies, published online by the journal Nature, give strong support to each side of the simmering debate. The work with embryonic stem cells, by Dr. Ron McKay and colleagues at the N.I.H., shows how the cells can be forced in the test tube, with special genes and signals, to morph into nerve cells that produce dopamine, a critical brain chemical. Those neurons are lost in Parkinson's disease.

Because embryonic cells grow vigorously in laboratory glassware, Dr. McKay's work is proof of the principle that unlimited amounts of specific human cell types for therapy could be generated from embryonic stem cells.

The other study, by Dr. Verfaillie (pronounced vair-fie-ee) and colleagues at the University of Minnesota, is of broad general significance. Reversing previous wisdom about adult stem cells, which holds that each type can renew just the cells of its own tissue, Dr. Verfaillie's team has derived from bone marrow an adult stem cell that seems to have all the versatility of embryonic stem cells.

"The findings are absolutely startling," said Dr. on, a stem cell expert at the University of Michigan.

The cells, which Dr. Verfaillie calls MAP cells, for multipotent adult progenitor, can form the principal types of mature body cells in glassware. When the mouse version of MAP cells are injected into a mouse embryo, they help form all the tissues of the body, just as embryonic cells do.

It seems that the MAP cells could in principle do everything expected of embryonic stem cells, with two extra advantages. They do not form a spontaneous tumor known as a teratoma, a serious hazard of therapy with embryonic stem cells, and they could in many cases be derived from the patient to be treated. Being the patient's own cells, they would be at no risk of immune rejection.

Opponents of using embryonic stem cell are quite likely to cite Dr. Verfaillie's findings to support their argument that cell therapy can be based on adult stem cells alone. Dr. Verfaillie, along with many other biologists, rejected that argument, saying at this stage both types of cell should be studied in parallel so that scientists can figure out which type offers the most promise for which disease.

A bill to ban therapeutic cloning, a proposed technique for turning any mature human cell back to the embryonic state, stalled in the Senate this month and seems dead for now.

The co-publication of Dr. Verfaillie and Dr. McKay's articles seems intended to blunt the MAP cell threat to embryonic stem cells by showing that the embryonic types are close to supplying a fundamental treatment of Parkinson's disease. But at a news conference today in Minneapolis, an editor at Nature, DeWitt, declined to confirm that this was the case.

Ms. DeWitt said that the two articles had been submitted within two weeks of each other and that in terms of influencing the Senate debate it was "very difficult to publish any stem cell paper at a time when there is not a political debate in the United States."

Nature, based in London, is owned by the Holtzbrinck publishing group of Stuttgart, Germany.

Dr. Verfaillie's finding is something of a bombshell to stem cell researchers. She has been working quietly on MAP cells for five years and announced her results at a conference in December. Her article in Nature is one of her first publications. Because she has just started to distribute her cells to other laboratories, no one in the United States has had time to repeat her experiments.

Stem experts say Dr. Verfaillie's results need to be confirmed by others.

"It's a paper by a single lab," said Dr. Fred H. Gage, an expert on brain stem cells at the Salk Institute in San Diego. "Truth has many faces, and in science it's independent confirmation in other labs."

Dr. Irving Weissman, who studies blood-forming stem cells at Stanford University, said of Dr. Verfaillie's work: "If it turns out to be true, it's very important. The key is for her to get her cell lines out to me and others so we can test whether they are pluripotent or not."

Pluripotent means the ability to form almost all the other cell types of the body, as embryonic stem cells can.

Dr. Verfaillie, saying she was trying to have her cells distributed as soon as possible, added that a group in Japan had already confirmed part of her work.

One of the first diseases that she hopes to treat with the cells is Hurler syndrome, a rare genetic abnormality that results in the loss of a single critical enzyme in the body and causes skeletal problems and severe mental retardation. No good therapy exists for the syndrome.

Another disease is muscular dystrophy, in which she hopes that MAP cells from a donor could be injected into the bloodstream and would engraft into muscles. Such therapies would require years of preparatory work, she said.

Dr. Gil van Bokkelen, chief executive of a biotechnology company in Cleveland, Athersys, said that his company had an option to become the exclusive licensee of all the stem cell findings made in Dr. Verfaillie's laboratory and that he hoped clinical trials could begin in 12 to 18 months.

Dr. Verfaillie said that there had been "extensive discussions with Athersys, but it isn't a done deal at this point in time."

The experiments she reported in Nature were with MAP cells from mice. The researcher said she had also derived MAP cells from people and could reliably do so with 80 percent of patients. She is working to understand the problem with the remaining 20 percent.

Dr. Verfaillie found the cells by accident, in the course of trying to culture mesenchymal stem cells. The cells, which are found in bone marrow, renew bone and cartilage. She noticed that after the mesenchymal stem cells died off, another cell remained, the MAP cells.

Copyright 2002 The New York Times Company