Endothelial Progenitor Cells Conditioned Medium Supports Number of GABAergic Neurons and Exerts Neuroprotection in Cultured Striatal Neuronal Progenitor Cells

Abstract

There is growing evidence that stem and progenitor cells exert regenerative actions by means of paracrine factors. In line with these notions, we recently demonstrated that endothelial progenitor cell (EPC)-derived conditioned medium (EPC-CM) substantially increased viability of brain microvascular cells. In the present study, we aimed at investigating whether EPC-CM supports cell survival of cultured striatal progenitor cells. For that purpose, primary cultures from fetal rat embryonic (E14) ganglionic eminence were prepared and grown for 7 days in vitro (DIV). EPC-CM was administered from DIV5–7. Treatment of the striatal cultures with EPC-CM resulted in significantly increased densities of GABA-immunoreactive (-ir) neurons. Inhibition of mitogen-activated protein kinase and phosphatidylinositol-3-kinase, but not of the ROCK pathway, significantly attenuated the EPC-CM induced increase in GABA-ir cell densities. Similar results were observed when EPC-CM was subjected to proteolytic digestion and lipid extraction. Furthermore, inhibition of translation abolished the EPC-CM induced effects. Importantly, EPC-CM displayed neuroprotection against 3-nitropropionic acid induced toxicity. These findings demonstrate that EPC-derived paracrine factors substantially promote survival and/or differentiation of cultured striatal progenitor cells involving both proteinaceous factors and lipidic factors. In sum, EPC-CM constituents might lead to a novel cell-free therapeutic strategy to challenge neuronal degeneration.