Abstract 1053: Identification Of A Novel Type Of Circulating Progenitor Cells Resembling Multipotent Mesoangioblasts From Peripheral Blood Of Children
Circulating progenitor cells contribute to neovascularization and have been used for cell therapy of ischemia. Endothelial progenitor cells (EPC) isolated from adult blood are characterized by coexpression of hematopoietic and endothelial markers, analogue to the hemangioblast. In contrast, in embryonic development, vessel-associated multipotent progenitors, the so called mesoangioblasts (MAB), have been experimentally described. MAB express the key marker of angiopoietic progenitors, KDR, as well as mesenchymal markers. In order to assess the phenotype and functional properties of circulating progenitors during postnatal development, we isolated cells from peripheral blood of children between 8 days and 2.5 years after birth and compared these cells with adult EPC. Isolated mononuclear cells were plated on fibronectin-coated dishes in EBM medium supplemented with growth factors. At day 14, adherent cells derived from children demonstrated expression of mesenchymal markers CD13, CD73, the endothelial markers CD105, KDR and VE-cadherin, but were negative for hematopoietic markers CD133 and CD45 as documented by FACS analysis and RT-PCR. In contrast, adult EPC did express hematopoietic and endothelial markers, but lacked expression of CD73. Thus, the children-derived circulating progeniors (ChCP) resemble the previously described multipotent MAB. Indeed, ChCP could be induced to differentiate to cardiomyocytes, smooth muscle cells, and osteoblasts. Moreover, ChCP did express the stem cell markers islet-1 and c-kit and showed a marked proliferative capacity (28.3±0.9 passages, 64.0±2.9 population doublings) before entering a senescent state. Population doubling was strongly correlated with age of donors (R2=0.824, p=0.0001). Consistently, ChCP had a high telomerase activity (OD 0.6±0.1) and secreted high levels of cytokines such as HGF, VEGF, and SDF-1. These data identify a novel circulating progenitor cells, which can be isolated during postnatal development in humans. These ChCP resemble the previously described multipotent MAB during embryonic development, exhibit a high proliferative capacity and express various functional stem cell markers. These progenitors might be well suited for cell therapeutic strategies.