Significant advances in our understanding of the role of bone marrow-derived cells in the formation of new vascu-lature have occurred in the last decade. Despite these advances, however, large gaps in our understanding of this biology remain. The population(s) of cells involved continue to be unresolved, and the methods of isolation of circulating endothelial progenitor cells remain to be standardized. There continues to be controversy regarding the importance of bone marrow-derived cells in neovasculature and the relative contribution of vasculogenesis versus angio-genesis in the adult. Other important questions such as a detailed description of the mechanisms of homing to areas of vascular growth and the role and ultimate fate of the endothelial progenitor cells that have incorporated into neo-vasculature in vivo remains to be elucidated. It is becoming clear that understanding the biology of circulating endo-thelial progenitor cells is critical to understanding the mechanisms of vessel formation, a process important in many pathological and physiological processes. Continued

Further Reading

Asahara, T., and Isner, J. M. (2002). State-of-the-art reviews on vascular stem cells and angiogenesis. J. Hematotherapy Stem Cell Res. 11, 171-178.

Asahara, T., Murohara, T., Sullivan, A., Silver, M., van der Zee, R., Li, T., Witzenbichler, B., Schatteman, G., and Isner, J. M. (1997). Isolation of putative progenitor endothelial cells for angiogenesis. Science 275, 964-967. The initial description of circulating endothelial progenitor cells in the adult.

Lyden, D., Hattori, K., Dias, S., Costa, C., Blaikie, P., Butros, L., Chadburn, A., Heissig, B., Marks, W., Witte, L., Wu, Y., Hicklin, D., Zhu, Z., Hackett, N. R., Crystal, R. G., Moore, M. A. S., Hajjar, K. A., Manova, K., Benezra, R., and Rafii, S. (2001). Impaired recruitment of bone-marrow-derived endopthelial and hematopoietic precursor cells blocks tumor angiogenesis and growth. Nat. Med. 7, 1194-1201. An important study demonstrating the necessity of bone marrow—derived cells for the formation of tumor vasculature.

Moldovan, N. I. (ed.) (2003). Novel Angiogenic Mechanisms: Role of Circulating Progenitor Endothelial Cells. New York: Klumer Academic/Plenum Publishers. A complete monograph detailing the role EPCs derived from monocytes in vascular growth.

Rabbany, S. Y., Heissig, B., Hattori, K., and Rafii, S. (2003). Molecular pathways regulating mobilization of marrow-derived stem cells for tissue revascularization. Trends Mol. Med. 9, 109-117. Excellent review of the known factors that effect EPC mobilization.

Rafii, S., Lyden, D., Benezra, R., Hattori, K., and Heissig, B. (2002). Vascular and hematopoietic stem cells: Novel targets for anti-angiogenesis therapy. Nat. Rev. Cancer 2, 826-835.

Szmitko, P. E., Fedak, P. W. M., Weisel, R. D., Stewart, D. J., Kutryk, M. J. B., and Verma, S. (2003). Endothelial progenitor cells: New hope for a broken heart. Circulation. 107, 3093-3100. Describes current clinical trials using EPCs.

Capsule Biographies

Dr. Fine is Chief of the Neuro-Oncology Branch of the National Cancer Institute and The National Institutes of Neurological Disorder and Stroke at the NIH. His laboratory focuses on the development of novel therapeutic strategies, including antiangiogenic approaches, for primary brain tumors.

Dr. Glod is Assistant Professor of Pediatrics in the Division of Pediatric Hematology/Oncology at The Cancer Institute of New Jersey and The University of Medicine and Dentistry of New Jersey. His research focuses on the role of bone marrow-derived cells in the growth and repair of vascula-ture in the brain.

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