CD34+ Cells Represent Highly Functional Endothelial Progenitor Cells in Murine Bone Marrow

Abstract

BackgroundEndothelial progenitor cells (EPCs) were shown to have angiogenic potential contributing to neovascularization. However, a clear definition of mouse EPCs by cell surface markers still remains elusive. We hypothesized that CD34 could be used for identification and isolation of functional EPCs from mouse bone marrow.Methodology/Principal FindingsCD34+ cells, c-Kit+/Sca-1+/Lin− (KSL) cells, c-Kit+/Lin− (KL) cells and Sca-1+/Lin− (SL) cells were isolated from mouse bone marrow mononuclear cells (BMMNCs) using fluorescent activated cell sorting. EPC colony forming capacity and differentiation capacity into endothelial lineage were examined in the cells. Although CD34+ cells showed the lowest EPC colony forming activity, CD34+ cells exhibited under endothelial culture conditions a more adherent phenotype compared with the others, demonstrating the highest mRNA expression levels of endothelial markers vWF, VE-cadherin, and Flk-1. Furthermore, a dramatic increase in immediate recruitment of cells to the myocardium following myocardial infarction and systemic cell injection was observed for CD34+ cells comparing with others, which could be explained by the highest mRNA expression levels of key homing-related molecules Integrin β2 and CXCR4 in CD34+ cells. Cell retention and incorporation into the vasculature of the ischemic myocardium was also markedly increased in the CD34+ cell-injected group, giving a possible explanation for significant reduction in fibrosis area, significant increase in neovascularization and the best cardiac functional recovery in this group in comparison with the others.ConclusionThese findings suggest that mouse CD34+ cells may represent a functional EPC population in bone marrow, which could benefit the investigation of therapeutic EPC biology.

Reversing Resistance to Vascular-Disrupting Agents by Blocking Late Mobilization of Circulating Endothelial Progenitor Cells

“…2C). These data were consistent with our (42), and importantly, vascular endothelial (VE)-cadherin, which directly supports the endothelial phenotype (Supplementary Fig. S2).…”

Extrarenal Progenitor Cells Do Not Contribute to Renal Endothelial Repair

“…[13][14][15] Therefore, CD34+ or mononuclear cells were isolated from blood or BM and cultured in colony-forming assays. 5,11,[16][17][18][19] Isolated EC-CFU cells were characterized by expression of the endothelial markers CD34, VEGFR2, CD31, CD146, and CD105, and also hematopoietic surface markers such as CD133, CD45, CD14, and CD115. In contrast, ECFCs were negative for hematopoietic surface markers and showed clonal proliferative potential and vessel formation capability in vitro and in vivo.…”

Hematopoietic stem cells are a critical sub-population of whole bone marrow in the treatment of myocardial infarction

“…+ cells have been shown to exhibit EPC characteristics [34], and EPC are known to have proangiogenic effects which can positively affect the outcome of ischemia [22].…”