Conditioned Medium from Endothelial Progenitor Cells promotes number of dopaminergic neurons and exerts neuroprotection in cultured ventral mesencephalic neuronal progenitor cells

Abstract Transplantation of stem and progenitor cells offers a promising tool for brain repair in the context of neuropathological disorders including Parkinson’s disease. There is growing proof that the capacity of adult stem and progenitor cells for tissue regeneration relies rather on the release of paracrine factors than on their cell replacement properties. In line with this notion, we have previously reported that conditioned medium (CM) collected from cultured Endothelial Progenitor Cells (EPC) stimulated survival of striatal neurons. In the present study we investigated whether EPC-CM promotes survival of cultured midbrain progenitor cells. For that purpose primary cultures from fetal rat embryonic ventral mesencephalon (VM) were prepared and grown for 7 days in vitro (DIV). EPC-CM was administered from DIV5-7. First, we found that EPC-CM treatment resulted in significantly increased cell densities of TH-ir neurons. Interestingly, this effect was no longer seen after proteolytic digestion of the EPC-CM. EPC-CM also significantly increased densities of beta-III-tubulin positive neurons and lba-1-ir microglial cells. The effect on dopaminergic neurons was not due to higher cell proliferation as no incorporation of EdU was observed in TH-ir cells. Importantly, EPC-CM exerted neuroprotection against MPP+ induced toxicity as in vitro model of Parkinson’s disease. Taken together, our findings identified EPC-CM as a powerful tool to promote survival of cultured VM neurons and further support the importance of paracrine factors in the actions of stem and progenitor cells for brain repair.