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Stanford Report, October 22, 2003

Bone marrow, nerve cell fusion may repair damage The research points to possible cellular ‘rescue’ mechanism


By AMY ADAMS

Bone marrow cells can fuse with specialized brain cells, possibly bolstering the brain cells or repairing damage, according to research from the School of Medicine.

This finding helps resolve an ongoing debate: Do adult stem cells transform from bone marrow cells into other cell types, such as brain, muscle or liver cells, or do they fuse with those cells to form a single entity with two nuclei? The research shows that for complex brain cells called Purkinje cells, fusion is the normal pathway.

This Purkinje cell glows brightly after fusing with a bone marrow cell that produces a fluorescent protein. Helen Blau’s research on this type of fusion appeared in the online edition of Nature Cell Biology. Photo: Courtesy of Helen Blau

Helen Blau, PhD, the Donald E. and Delia B. Baxter Professor of Pharmacology, had previously shown that transplanted bone marrow cells can wind their way up to the brain in humans where they take on characteristics of Purkinje cells — large cells in the part of the brain that controls muscular movement and balance. She had also shown that mature cells in a lab dish can fuse with other cell types and take on characteristics of those cells.

In her most recent work, published in the Oct. 16 advance online issue of Nature Cell Biology, Blau showed that the bone marrow cells in mice fuse with existing Purkinje cells and activate genes normally made in Purkinje cell nuclei. The work will also be published in the November issue of the journal.

This paper appeared at the same time that a group from UC-San Francisco had similar findings published in the online edition of the journal Nature. Together, these findings provide strong evidence that bone marrow cells fuse with Purkinje cells rather than transform into a different cell type.

"I think that fusion might be a really important biological mechanism," Blau said. She said researchers previously considered fusion to be less medically important than the idea that bone marrow cells may be able to change fates entirely. Blau disagrees with that assessment. "Fusion might be a sophisticated mechanism for rescuing complex damaged cells," she said.

Blau and senior research scientist James Weimann, PhD, transplanted mice with bone marrow cells that had been genetically altered to produce a fluorescent green protein. Over the course of the next 18 months (75 percent of a mouse’s life span), they looked for signs of fluorescent green cells in the animals’ brains.

Over time, the group found an increasing number of Purkinje cells that glowed green under a microscope. Looking closely at these cells, they found two nuclei - one from the original Purkinje cell and one from the fused bone marrow cell. They also found that the compact nucleus of the bone marrow cell expanded over time to take on the appearance of the more loosely packed Purkinje cell nucleus.

The bone marrow nucleus in the fused cell also acts like a Purkinje cell nucleus, they found. When the group transplanted mice with bone marrow cells that only produce green protein when Purkinje cell genes are active, they discovered fluorescent green Purkinje cells. This showed that the bone marrow cells had fused with Purkinje cells and activated Purkinje cell genes.

Blau said the next step is to learn under what circumstances bone marrow cells fuse with Purkinje cells. "If you know what those signals are, you could deliver the signal to damaged tissue and recruit the body’s own bone marrow cells to treat disease." Blau hopes these recruited bone marrow cells may be a way of repairing damage caused by injury, stroke or Parkinson’s disease.

Other study participants include postdoctoral scholar Clas Johansson, PhD, and research associate Angelica Trejo.



Bone marrow cells take on new role in the brain (2/5/03)

Baxter Lab opens its doors onto medical research (5/22/02)