Objective - Emerging evidence suggests that human blood contains bone marrow (BM)-derived endothelial progenitor cells that contribute to postnatal neovascularization. Clinical trials demonstrated that administration of BM-cells can enhance neovascularization. Most studies, however, used crude cell populations. Identifying the role of different cell populations is important for developing improved cellular therapies. Methods and Results - Effects of the hematopoietic stem cell-containing CD34+ cell population on migration, proliferation, differentiation, stimulation of, and participation in capillary-like tubule formation were assessed in an in vitro 3-dimensional matrix model using human microvascular endothelial cells. During movement over the endothelial monolayer, CD34+ cells remained stuck at sites of capillary tube formation and time- and dose-dependently formed cell clusters. Immunohistochemistry confirmed homing and proliferation of CD34+ cells in and around capillary sprouts. CD34+ cells were transduced with the LNGFR marker gene to allow tracing. LNGFR gene-transduced CD34 + cells integrated in the tubular structures and stained positive for CD31 and UEA-1. CD34+ cells alone stimulated neovascularization by 17%. Coculture with CD34- cells led to 68% enhancement of neovascularization, whereas CD34- cells displayed a variable response by themselves. Cell-cell contact between CD34+ and CD34- cells facilitated endothelial differentiation of CD34+ cells. Conclusions - Our data suggest that administration of CD34+-enriched cell populations may significantly improve neovascularization and point at an important supportive role for (endogenous or exogenous) CD34- cells.

Angiogenesis, Gene therapy, Nitric oxide, endothelium, vascular type, Peripheral vascular disease
dx.doi.org/10.1161/01.ATV.0000177808.92494.14, hdl.handle.net/1765/67569
Arteriosclerosis, Thrombosis, and Vascular Biology
Department of Immunology

Rookmaaker, M.B, Verhaar, M.C, Loomans, C.J.M, Verloop, H, Peters, E, Westerweel, J, … van Hinsbergh, V.W.M. (2005). CD34+ cells home, proliferate, and participate in capillary formation, and in combination with CD34- cells enhance tube formation in a 3-dimensional matrix. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(9), 1843–1850. doi:10.1161/01.ATV.0000177808.92494.14