Banking on Bone Marrow

by Paul Muhlrad on November 1, 2005 - 11:40am

QUEST Vol. 12, No. 6

Affiliation
Baylor College of Medicine,
Houston

Strategy
Coaxing bone marrow cells to fuse with muscle fibers

Status
Laboratory experiments

Margaret Goodell, Ph.D.
Margaret Goodell, PH.D.

Molecular biologist Margaret Goodell, an MDA research grantee at Baylor College of Medicine in Houston, became interested in muscular dystrophy through her long-standing research on blood cell regeneration.

Since 2002, she’s been an associate professor at Baylor’s Center for Cell and Gene Therapy, where she received a Michael E. DeBakey Excellence in Research Award last year.

Goodell, born in Baltimore in 1965, completed a doctoral degree in biology in 1991 at the University of Cambridge in England. She then relocated to Cambridge, Mass., to begin postdoctoral research at the Whitehead Institute for Biomedical Research, studying cells that form blood.

Blood cells regenerate from stem cells found in the bone marrow, she explains. “We became interested in the possibility that you could use bone marrow stem cells for the regeneration of other tissues.”

Goodell’s lab studies a type of bone marrow cell called a hematopoietic stem cell (HSC). Normally, hematopoietic (blood-forming) cells generate the many different types of red and white blood cells.

But over the past five years, a number of laboratories, including Goodell’s, have reported that, in very rare instances, HSCs also appear to convert to mature muscle cells. “What we’re trying to do is find out why it’s at a low efficiency and see if we can boost that efficiency,” she says.

To detect the conversion, researchers typically place stem cells that have been tagged with a visible marker, such as a fluorescent protein, into a laboratory mouse or a tissue culture dish growing muscle cells.

“If you stimulate the muscle to regenerate, you will see that a small proportion of the muscle cells have incorporated the fluorescent tag,” indicating that the stem cells have become muscle cells, Goodell explains.

The research is still in its infancy, and researchers continue to debate the means by which the bone marrow cells turn into muscle. Some scientists think the stem cells’ genetic program becomes “rewired” so that, instead of maturing into blood cells, they become muscle cells. But Goodell suspects something else may be happening.

“My lab thinks that it’s fusion — that some type of blood-borne cell fuses to the muscle cells.” Whatever the mechanism, the bottom line, Goodell says, is that bone marrow cells or their descendants can wind up in the muscle. And this may offer a path to therapy for people with muscle diseases.

Goodell’s team has homed in on a particular type of bone-marrow-derived blood cell — the macrophage — which they think is the predominant blood cell type that fuses with muscles.

Macrophages are large, amoebalike cells that crawl through the tissues of the body, scavenging bacteria and other foreign particles. They often fuse with one another, and muscles normally grow by the fusion of muscle stem cells to mature muscle fibers. So, Goodell says, it’s reasonable that macrophages might also fuse with muscle cells, and experiments in her lab support that notion.

“We’ve been, first of all, trying to identify proteins that are involved in the fusion between the macrophage and the muscle cell, and we’re trying to see whether their expression can be modulated to enhance the process’s efficiency.”

There’s still much to be learned before Goodell’s research reaches patients. “If it ever does lead to a therapy, we’re probably talking about at least 10 years,” she cautions.

Nonetheless, she’s excited at the prospect of treating muscular dystrophy with blood cells. “It’s a way to get at virtually all of the muscles in the body, not just the major ones that we can see. Every muscle fiber is fed by the bloodstream in one way or another, so if you can really get something delivered through the bloodstream rather than in some localized way, it’s potentially a very powerful therapy.”

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