Novel Role of ER Stress and Mitochondria Stress in Serum-deprivation Induced Apoptosis of Rat Mesenchymal Stem Cells.

Abstract

The poor survival of mesenchymal stem cells (MSCs) compromises the efficacy of stem cell therapy. Growth factor deprivation is one of the important factors that have challenged the survival of donor MSCs in cell therapy. In this study, the aim was to evaluate the effect of serum deprivation on the cell death of MSCs and to investigate the underlying mechanisms. Apoptosis of MSCs was evaluated with Hoechst 33342/PI staining. Signaling pathways involved in serum-deprivation induced apoptosis were analyzed using Western blotting. The results revealed that serum deprivation induced apoptosis in MSCs within 72 h of treatment. Serum deprivation was shown to lead to protein expression alterations in Bax, Bcl-2, casepase-3, casepase-8, GRP78, and CHOP during experiments. The data suggested that the mitochondria death pathway, the extrinsic apoptotic pathway and the endoplastic reticulum(ER) stress pathway were all involved in MSCs apoptosis. The increase in expression of CHOP and the simultaneous decrease in Bcl-2 expression suggest a synergistic effect in apoptosis induction in both the mitochondrion and the ER.