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

• DOI: 10.1016/j.neulet.2012.06.002
• Publication Date: 2012-06-12T18:34:32Z
• Authors: Shi-Jing Mo; Qian Zhong; Yan-Fang Zhou; David B. Deng; Xiu-Quan Zhang
• Keywords: Male; Neurons; Apoptosis; Bone Marrow Cells; Mesenchymal Stem Cells; Cobalt; PC12 Cells; Cell Hypoxia; Rats; Up-Regulation; Rats, Sprague-Dawley; 03 medical and health sciences; 0302 clinical medicine; Proto-Oncogene Proteins c-bcl-2; Cytoprotection; Caspases; Gene Knockdown Techniques; Animals; RNA, Small Interfering; Erythropoietin; Cells, Cultured

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 CoCl(2) via the production of erythropoietin (EPO). Addition of CoCl(2) 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 CoCl(2) in a ratio-dependent manner. To explore whether expression of EPO induced by CoCl(2) 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 CoCl(2), and the cytoprotective effect of BM-MSCs. Reverse transcriptase polymerase chain reaction results showed that EPO siRNA reversed upregulation of Bcl-2, Bcl-X(L) 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 CoCl(2) might be dependent on EPO expression, at least in part, via the regulation of Bcl-2 family members and caspases.