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CD34+ cells home, proliferate, and participate in capillary formation, and in combination with CD34- cells enhance tube formation in a 3-dimensional matrix

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Author: Rookmaaker, M.B. · Verhaar, M.C. · Loomans, C.J.M. · Verloop, R. · Peters, E. · Westerweel, P.E. · Murohara, T. · Staal, F.J.T. · Zonneveld, A.J. van · Koolwijk, P. · Rabelink, T.J. · Hinsbergh, V.W.M. van
Institution: TNO Kwaliteit van Leven
Source:Arteriosclerosis, Thrombosis, and Vascular Biology, 9, 25, 1843-1850
Identifier: 238685
doi: doi:10.1161/01.ATV.0000177808.92494.14
Keywords: Biology · Biomedical Research · Angiogenesis · Gene therapy · Nitric oxide, endothelium, vascular type · CD34 antigen · Nitric oxide · Bone marrow cell · Capillary endothelium · Capillary proliferation · Cell population · Cell proliferation · Facilitation · Gene therapy · Hhematopoietic stem cell · Human cell · Immunohistochemistry · Marker gene · Neovascularization (pathology) · Nerve sprouting · Neural tube · Peripheral vascular disease · Antigens, CD34 · Biological Markers · Capillaries · Cell Differentiation · Cell Division · Cell Movement · Cell Separation · Cells, Cultured · Coculture Techniques · Endothelium, Vascular · Fetal Blood · Hematopoietic Stem Cells · Humans · Neovascularization, Physiologic


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. © 2005 American Heart Association, Inc. Chemicals / CAS: nitric oxide, 10102-43-9; Antigens, CD34; Biological Markers