SAN FRANCISCO CHRONICLE (SF) - FRIDAY July 1, 1988 Edition: FINAL Section: NEWS Page: A1 Word Count: 907
David Perlman, Chronicle Science Editor

Although their first results in isolating and purifying the cells, known as T-cells, have involved only laboratory mice, the scientists said that they are already experimenting to achieve the same feat for similar human cells.

The ultimate consequence of the research in future years, according to the leader of the Stanford group, could be a varied array of new approaches to the treatment of many diseases:

-- Hazardous bone marrow transplants might be made far safer in treating leukemia and other cancers.

-- Gene therapy could become possible for many hereditary diseases.

-- Blood disorders such as sickle cell anemia could be corrected.

-- Rebuilding the immune system after infection by the AIDS virus might become possible.

-- Lives might be saved after overexposure to deadly doses of radiation.

The research should also lead to the deepest understanding yet of how the immune system develops in both animals and humans and how the eight or nine different types of cells that circulate in the bloodstream are formed.

The Stanford researchers, led by Dr. Irving Weissman, a pathologist and cancer biologist, are reporting their success in today's issue of the journal Science.

The versatile mouse cells that have been purified from the animals' marrow are vitally important because they are the progenitors of all the differentiated cells of the immune system: the helper T-cells, the killer cells, the B-cells that produce antibodies and the macrophages that scavenge and devour invading viruses and bacteria.

The stem cells in the marrow also give rise to all the normal red cells and platelets that sustain life as they circulate in the bloodstream.

Marrow transplants are often used to repair cell damage caused by exposure to heavy doses of radiation. In their experiments, Weissman and his colleagues found they could save the lives of all the mice they dosed with lethal bursts of radiation by injecting them after exposure with fewer than 100 stem cells. Only 30 stem cells were enough to save half the lethally irradiated mice, the group reported.

Injections of the purified stem cells into the irradiated mice also successfully reconstituted all their red and white blood cells within a few days, Weissman said.

His team identified the specific cells that the stem cells created - the T and B cells, the red cells, the macrophages and the others - by removing the spleens and thymus glands of the animals and assaying the numbers of the new specialized cells. Tests also showed that the reconstituted immune systems of the mice functioned normally.

A single stem cell reaching the thymus gland of an animal - and presumably a human - multiplies and renews itself over and over again, and gives rise to anywhere from a million to 10 million well-functioning cells of the immune system, Weissman explained in an interview. But just how this all happens is still something of a mystery.

"The thymus," he said, "is really a place that seems to educate the stem cells - it instructs them how to differentiate and what roles to play in immunity. But how the thymus does it is entirely unknown."

Presumably, he said, some environmental factor inside the thymus controls the transformation of the stem cells into the many varied cells of the immune system.

In their report, Weissman and his colleagues noted that the strategy they have used to identify and isolate the stem cells of mice could in principle also be applied to human cells.

The team is working toward that end and is seeking a way to assess the effectiveness of transplanted human stem cells without the obviously unacceptable process of removing the thymus gland or the spleen.

Treating human diseases by stem cell transplants may be years away, but the possibilities are varied and exciting, Weissman said.

In human transplants of whole marrow for such lethal problems as leukemia or radiation damage, the tissue of the donor and the recipient must be closely matched. Otherwise, the white blood cells of the donor marrow can attack the recipient's tissues in a deadly reverse form of immune reaction known as graft-vs.-host disease.

Weissman's hope is that by transplanting purified human stem cells instead of whole bone marrow containing mixed batches of marrow cells, this dangerous problem can be avoided.

Another possible role for purified human stem cells, Weissman said, could be in gene therapy to correct hereditary blood disorders.

A small number of stem cells would be removed from patients with the genetic defects; the cells would be equipped in the laboratory with genetically engineered corrective genes and the stem cells would then be returned to the patient to create a new and defect-free blood system, Weissman said.

Recent evidence has shown that the AIDS virus, known as HIV, can infect bone marrow, and the thymus gland may also be involved. "If so," Weissman said, "then the only way to get a clean immune system after AIDS infection might be to transplant stem cells."

Weissman's colleagues in the long-term basic research project were Dr. Shelly Heimfeld, a postdoctoral fellow in Stanford Medical School's laboratory of experimental oncology, and Dr. Gerald J. Spangrude, who is now at the Royal Melbourne Hospital in Australia.

CAPTION: GRAPHIC - IMPORTANCE OF STEM CELLS

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