Monday, June 30, 2003

By Anita Srikameswaran, Post-Gazette Staff Writer

Researchers at Children's Hospital have found that a unique population of mouse stem cells that make muscle fibers can be used to replenish the blood system like a bone marrow transplant and then revert back to their muscle-making ways.

You could call it muscle memory of stem cells.

Molecular biologist Johnny Huard said the experiments by his research team provide the strongest evidence yet that muscle stem cells have the ability to develop from one cell type into another and back again, a characteristic scientists refer to as plasticity.

Huard and his colleagues report their findings in next month's issue of the journal Nature Cell Biology.

Stem cells found in embryos are thought to be capable of generating a wide variety of cell types. But scientists are still debating whether stem cells found in adults hold the same promise. Some authorities say that the adult types are less useful because they cannot generate as many different kinds of cells and they are closer to the end of their lifespan.

But Huard's results with adult muscle stem cells are interesting and further investigation is warranted, said Massimo Trucco, a diabetes expert at Children's Hospital.

In the experiments, muscle stem cells were injected into mice whose bone marrow was destroyed with radiation. The animals survived because the transplanted cells became bone marrow cells, which in turn produced new blood cells, Huard said. Mice that were irradiated but didn't get the cell transplant died within 17 days.

Then the researchers threw in a twist. They recovered donor bone marrow cells from the treated mice and put them in a flask with a standard growing medium. Without any other chemical prompting, the blood cells went back to their true calling, namely making muscle fibers.

"This is why we really believe they have memory somehow," Huard said. "Clinically, this is not a major advantage, but scientifically it's very interesting."

Medical applications could develop, however. Potentially, cancer patients who need bone marrow transplants could use their own healthy muscle stem cells as a source, rather than relying on finding a matching donor and risking rejection, Trucco explained. The muscle stem cells might be easier to harvest than bone marrow cells and be less likely to contain malignant cells.

Also, earlier experiments have indicated that Huard's cells don't trigger an immediate immune response, which could make them good candidates to encourage tolerance of transplanted organs.

Huard and Trucco will be working together to see if the cells can generate functional insulin-secreting cells of the pancreas, which could be used to treat diabetes. Huard is currently trying to isolate the human counterpart of the mouse muscle stem cell.

Anita Srikameswaran can be reached at anitas@post-gazette.com or 412-263-3858.