R Periasamy

The Cytoprotective Effects of Human Endothelial Progenitor Cell-Conditioned Medium Against an Ischemic Insult Are Not Dependent on VEGF and IL-8.

Endothelial progenitor cells (EPCs) promote revascularization and tissue repair mainly by paracrine actions. In the present study, we investigated whether EPC-secreted factors in the form of conditioned medium (EPC-CM) can protect cultured brain microvascular endothelial cells against an ischemic insult. Furthermore, we addressed the type of factors that are involved in the EPC-CM-mediated functions. For that purpose, rat brain-derived endothelial cells (rBCEC4 cell line) were exposed to EPC-CM pretreated with proteolytic digestion, heat inactivation, and lipid extraction. Moreover, the involvement of VEGF and IL-8, as canonical angiogenic factors, was investigated by means of neutralizing antibodies. We demonstrated that EPC-CM significantly protected the rBCEC4 cells against an ischemic insult mimicked by induced oxygen–glucose deprivation followed by reoxygenation. The cytoprotective effect was displayed by higher viable cell numbers and reduced caspase 3/7 activity. Heat inactivation, proteolytic digestion, and lipid extraction resulted in a significantly reduced EPC-CM-dependent increase in rBCEC4 viability, tube formation, and survival following the ischemic challenge. Notably, VEGF and IL-8 neutralization did not affect the actions of EPC-CM on rBCEC4 under both standard and ischemic conditions. In summary, our findings show that paracrine factors released by EPCs activate an angiogenic and cytoprotective response on brain microvascular cells and that the activity of EPC-CM relies on the concerted action of nonproteinaceous and proteinaceous factors but do not directly involve VEGF and IL-8.

In vitro-microenvironment directs preconditioning of human chorion derived MSC promoting differentiation of OPC-like cells

The loss of oligodendrocyte progenitor cells (OPC) is a hallmark of perinatal brain injury. Our aim was to develop an in vitro culture condition for human chorion-derived mesenchymal stem cells (MSC) that enhances their stem cell properties and their capability to differentiate towards OPC-like cells. MSC were grown either in serum replacement medium (SRM) or serum-containing medium (SM) and tested for their morphology, proliferation, secretome, migration, protein expression and differentiation into OPC-like cells. MSC cultured in SRM condition have distinct morphology/protein expression profile, increased cell proliferation/migration and capacity to differentiate into OPC-like cells.