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(Circulation Research. 2005;97:1027.)
© 2005 American Heart Association, Inc.

Cellular Biology

Mobilization of Bone Marrow–Derived Cells Enhances the Angiogenic Response to Hypoxia Without Transdifferentiation Into Endothelial Cells

Thomas J. O’Neill, IV, Brian R. Wamhoff, Gary K. Owens, Thomas C. Skalak

From the Department of Molecular Physiology and Biological Physics (T.J.O., B.R.W., G.K.O.) and Department of Biomedical Engineering (T.J.O., T.C.S.), University of Virginia, Charlottesville.

Correspondence to Gary K Owens, PhD, Dept of Molecular Physiology and Biological Physics, University of Virginia, PO Box 800736, Charlottesville, VA 22908-0736. E-mail gko{at}virginia.edu

Bone marrow–derived cells (BMCs) have been implicated as a modifiers of vascular growth either directly by transdifferentiation into endothelial cells (ECs) or indirectly through growth factor release. To examine these possibilities under physiological conditions, we developed a model of hypoxia-mediated angiogenesis in the mouse spinotrapezius muscle. This allows whole-mount analysis; therefore, the morphology and location of BMCs within the vascular network may be observed along with differentiation markers. We exposed bone marrow transplant chimeric mice to hypoxia and treated a subset with granulocyte macrophage colony–stimulating factor. Exposure to hypoxia caused an 13% increase in capillary density relative to control. Hypoxia did not increase the overall number of muscle-resident BMCs, but did increase the number of rounded BMCs by 25%. There was no discernable BMC contribution to the endothelium, although some BMCs assumed a pericyte morphology around capillaries. Granulocyte macrophage colony–stimulating factor treatment further increased the number of round BMCs within the muscle and caused a 23% increase in angiogenesis. The results of this study suggest a potentially beneficial action of BMCs during hypoxia through paracrine release of growth factors but not transdifferentiation into ECs.

Key Words: adult stem cells • angiogenesis • bone marrow • hypoxia

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