CD34+ cells home, proliferate, and participate in capillary formation, and in combination with CD34- cells enhance tube formation in a 3-dimensional matrix.
作者:
Rookmaaker(Maarten B),Verhaar(Marianne C),Loomans(Cindy J M),Verloop(Robert),Peters(Erna),Westerweel(Peter E),Murohara(Toyoaki),Staal(Frank J T),van Zonneveld(Anton Jan),Koolwijk(Pieter),Rabelink(Ton J),van Hinsbergh(Victor W M)
状态:
发布时间2005-08-29
, 更新时间 2015-11-19
期刊:
Arterioscler Thromb Vasc Biol
摘要:
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.,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.,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.