Dec. 2 - 15, 2005
Vol. 35, Issue 21
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Stem cells
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Stem cells
Study finds they are bosses, not workers, in tissue repair

This image illustrates the study’s findings. Here, mouse muscle tissue (the pink background color) has been injected with bone marrow (glowing green) from a different line of genetically controlled mice and exposed to an environment of restricted oxygen for 21 days. Restricting oxygen stimulated the bone marrow stem cells to move to positions near the blood vessel walls, but did not cause them to convert into endothelial or smooth muscle cells.

By Charlotte Crystal

For years, scientists believed that adult stem cells, under conditions of reduced oxygen — such as that found in victims of a heart attack or stroke — acted as building blocks by constructing new passageways for blood to bypass damaged tissue. However, a new study by a team of University of Virginia researchers suggests that stem cells act as construction supervisors, directing the work of other cells, rather than doing the heavy lifting themselves.

“Our findings indicate a new understanding of the role played by adult stem cells,” said Thomas Skalak, chairman of the Department of Biomedical Engineering, who along with his colleague Gary Owens, professor of molecular physiology, is leading the research team. “It’s a shift from a building role to a signaling role, orchestrating the repair and growth of damaged tissue.”

The research team’s findings suggest a new tack in the search for therapies for heart disease and peripheral artery disease.

“Our findings point to an alternative to the big pharma strategy of searching for blockbuster drugs,” Skalak said. “Instead, they suggest that a strategy of harnessing the body’s own reparative mechanisms could be more effective. Blockbuster drugs have been single molecules that target a single process, but the adult stem cells we studied appear to coordinate several processes in repair and growth, which single molecules have not been able to do.”

Tom Skalak
Photo by Rebecca Arrington
Thomas Skalak, a lead investigator of the stem cell research team.

The research team’s results are published in the current issue (released Nov. 11) of the peer-reviewed journal Circulation Research. The article, “Mobilization of Bone Marrow-Derived Cells Enhances the Angiogenic Response to Hypoxia Without Transdifferentiation Into Endothelial Cells,” was co-authored by Skalak and Owens with Thomas J. O’Neill IV, a doctoral candidate in molecular physiology in Skalak’s lab; and Brian R. Wamhoff, assistant research professor with U.Va.’s Department of Molecular Physiology and Biological Physics.

Circulation Research highlighted the importance of the U.Va. research findings to its readers by pairing the article with an editorial commenting on its findings. The editorial, “Tissue-Resident Bone Marrow-Derived Progenitor Cells Key Players in Hypoxia-Induced Angiogenesis,” was written by three other researchers in the field, Gwenaele Garin, Marlene Mathews and Bradford C. Berk with the Cardiovascular Research Institute and Department of Medicine at the University of Rochester Medical Center.

The study was supported by a Bioengineering Research Partnership grant and an MD/PhD Training grant to U.Va. from the National Institute of Health’s Heart, Lung, and Blood Institute.


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