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Stanford Report, February 5, 2003

Bone marrow cells take on new role in the brain

By AMY ADAMS

Researchers in the Baxter Laboratory at the medical center have published evidence showing that cells from the bone marrow may help repair or maintain other tissue cells.

A paper in this week’s online edition of Proceedings of the National Academy of Sciences describes finding chromosomes from a bone marrow transplant in brain cells of transplant recipients.

After a bone marrow transplant from a man, a cell in this woman’s brain contained both an X and a Y chromosome. Ordinarily she would have two X chromosomes. PHOTO: COURTESY OF BAXTER LABORATORY

When people receive a bone marrow transplant after high-dose chemotherapy, some of the transplanted cells regenerate the blood-making cells that were destroyed. In past experiments in mice, Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology, found that cells from the transplant could also relocate to tissues throughout the body rather than being restricted to the bone marrow and blood.

"Now we know that it can also happen in humans," said James Weimann, PhD, co-first author on the paper and a senior research scientist in Blau’s lab.

Blau, Weimann, and co-first author Carol Charlton, PhD, a research associate in the lab, studied brain samples from women who had chemotherapy to treat their leukemia and then later received bone marrow transplants from male donors. These samples were ideal for this experiment because the donor cells contained a Y sex chromosome whereas cells in the women contained only X chromosomes. Any Y chromosome that the researchers identified must have come from the transplant donor.

To look for the telltale Y chromosome, the researchers used molecules with a double identity. One part of the molecule could bind to either the X or Y chromosome, while the other part acted as a fluorescent molecular beacon. The molecule that bound the X chromosome had a red beacon whereas the Y-recognizing molecule had a green beacon. When they put these stains on the preserved samples, the X chromosomes glowed red and any Y chromosomes glowed green. Charlton then searched the samples under a microscope for green chromosomes in the brain tissue.

As expected, blood cells within the brain contained Y chromosomes because they were made by bone marrow cells from the transplant. The researchers also found five nerve cells called Purkinje cells — involved in controlling balance and movement — that contained Y chromosomes in addition to their original X chromosomes. These out-of-place chromosomes could only have come from male cells in the bone marrow transplant.

Blau suspects the Purkinje cells may have gotten their Y chromosome from a group of traveling bone marrow cells. "I think these cells may act as a repair squad," Blau said. The cells travel the bloodstream, respond to stress and repair damaged tissues such as brain, muscle and possibly others throughout the body. In some cases the bone marrow cells may fuse with damaged cells or they may transform to replace the cells.

She said the next steps are to learn which cells in the bone marrow act as the repair squad, how they are lured to tissues and how they repair damage once there.

"If we can learn what the signals are, we may be able to direct the repair cells to where they are needed," Blau said. "Wouldn’t it be terrific if we could enlist the body to treat its own disease?"

Blau said adult bone marrow cells may be useful for treating some diseases or some tissues but not others. "We need to study all types of stem cells," she said.

Timothy Brazelton, PhD, a graduate student in the lab, also contributed to this work.




Researchers track stem cells in the act of morphing (11/20/02)

Debate over stem cells is local
as well as national
(9/11/02)