γ03b3;-Irradiated cord blood MNCs: Different paracrine effects on mature and progenitor endothelial cells.

Cell-based therapies have been employed to promote neovascularization mainly through the release of paracrine factors inhibiting apoptosis and supporting migration and proliferation of resident differentiated cells. We tested in vitro pro-angiogenic effects of apoptotic cord blood-derived mononuclear cells (CB-MNCs) and their conditioned medium (CM) on mature endothelial cells (HUVECs) and peripheral blood-derived endothelial progenitor cells (ECFCs). CB-MNCs were γ03b3;-irradiated to induce apoptosis and cultured for 72h to obtain the release of CM. MNCs viability, evaluated by flow cytometry, decreased progressively after γ03b3;-irradiation reaching 41% at 72h. γ03b3;-Irradiated MNCs (γ03b3;MNCs) released increasing amounts of EGF, PDGF-AB and VEGF in their CM over time, as assessed by ELISA. γ03b3;-MNCs and their CM enhanced capillary-like network formation (in a dose-dependent and time-persistent manner), proliferation and migration of HUVECs in vitro, while they primed capillary-like network formation (dose-independent and not time-persistent) and induced migration but did not support proliferation of ECFCs. Our data support the hypothesis of paracrine mechanism as prevalent in regenerative medicine and demonstrate the efficacy of MNCs secretome in inducing neovascularization. To our knowledge, this is the first paper highlighting differential pro-angiogenic effects of CM on mature and progenitor endothelial cells, adding a tile in the understanding of mechanisms involved in neovascularization. [ABSTRACT FROM AUTHOR]