Bone Marrow Cells Take On New Role In The Brain, Say Stanford Researchers

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 at the School of Medicine, 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, first author on the paper and a senior research scientist in Blau's lab.

Blau and Weimann looked at brain samples taken from women who underwent 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 Blau and Weimann 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. Weimann 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. She added that in some cases the bone marrow cells might fuse with damaged cells while in other instances they 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 these cells are lured to tissues and how they repair damage once they get 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 added that adult bone marrow cells may be particularly useful for treating some diseases or some tissues but not others. "We need to study all types of stem cells," she said.

Other Stanford researchers who contributed to this work include Carol Charlton, PhD, a research associate, and graduate student Timothy Brazelton, PhD.