Systematic assessment in an animal model of the angiogenic potential of different human cell sources for therapeutic revascularization

Human cells employed were mononuclear cells from normal peripheral blood and HPC-rich cell sources (umbilical cord blood, mobilized peripheral blood, bone marrow), CD34+ enriched or depleted subsets of these, and outgrowth cell populations from these. An established sponge implant angiogenesis model was adapted to determine the effects of different human cells on vascularization of implants in immunodeficient mice. Angiogenesis was quantified by vessel density and species of origin by immunohistochemistry.CD34+ cells from mobilized peripheral blood or umbilical cord blood HPC were the only cells to promote new vessel growth, but did not incorporate into vessels. Only endothelial outgrowth cells (EOC) incorporated into vessels, but these did not promote vessel growth.These studies indicate that, since EPC are very rare, any benefit seen in clinical trials of HPC in therapeutic vascular regeneration is predominantly mediated by indirect proangiogenic effects rather than through direct incorporation of any rare EPC contained within these sources. It should be possible to produce autologous EOC for therapeutic use, and evaluate the effect of EPC distinct from, or in synergy with, the proangiogenic effects of HPC therapies.Circulating endothelial progenitor cells (EPC) were first recognized in 1997 [1,2], introducing the concept that circulating EPC might supplement local angiogenesis which had heretofore been viewed as arising solely by outgrowth from pre-existing vasculature. Thus EPC had potential for development of cell-based therapeutic angiogenesis. EPC in adults were proposed to share a common stem cell with hematopoietic progenitor cells (HPC)[3], and like HPC express CD34 and mobilize from bone marrow [1,2]. It was proposed that, in the absence of a precise phenotype definition, EPC would coincide with HPC. Consequently, development of therapy progressed rapidly through preclinical studies to early clinical studies by employing HPC sources as therapeutic cells o