Bone marrow-derived mesenchymal stem cells prevent the apoptosis of neuron-like PC12 cells via erythropoietin expression

Abstract

It is known that bone marrow-derived mesenchymal stem cells (BM-MSCs) are able to improve neuronal function through secretion of trophic factors in animal models of middle cerebral artery occlusion (MCAo). In this study, we demonstrated that incubation of BM-MSCs protects PC12 cells against apoptosis induced by CoCl2 via the production of erythropoietin (EPO). Addition of CoCl2 to BM-MSCs cultures induced the expression of EPO in a time-dependent manner. Additionally, BM-MSCs co-culture protected PC12 cells against apoptosis induced by CoCl2 in a ratio-dependent manner. To explore whether expression of EPO induced by CoCl2 is required for BM-MSCs-mediated cytoprotection, we transfected BM-MSCs with EPO small interfering RNA (siRNA). Knocking-down EPO abrogated increases in EPO expression induced by CoCl2, and the cytoprotective effect of BM-MSCs. Reverse transcriptase polymerase chain reaction results showed that EPO siRNA reversed upregulation of Bcl-2, Bcl-XL expression and downregulation of Bax, Bak, caspase-9, and caspase-3 expression. Our results revealed that the protective effect of BM-MSCs against PC12 cell apoptosis induced by CoCl2 might be dependent on EPO expression, at least in part, via the regulation of Bcl-2 family members and caspases.