Apelin 13: a novel approach to enhance efficacy of hypoxic preconditioned mesenchymal stem cells for cell therapy of diabetes.

Recent studies have proposed cell therapy as an alternative therapeutic strategy for many disease states such as diabetes mellitus. Among different cell types mesenchymal stem cells (MSC) have attracted a significant attention based on their intriguing potentials. However MSC therapy is limited as a large portion of transplanted cells undergo apoptosis after transplantation. Therefore, proposing a strategy to overcome this obstacle may be of great value. Recent studies have shown that hypoxia preconditioning (HPC) may improve cell viability after transplantation. Both HPC and hyperglycemia are reported to exert effects by different levels of ROS overproduction. Overdose of ROS in this case would trigger the apoptosis and thereby decreased cell viability after transplantation. Apelin; the endogenous ligand for the previously orphaned G protein-coupled receptor APJ is shown to exert anti apoptotic effects On oxidative stress-induced apoptosis in MSCs via MAPK/ERK1/2 and PI3K/AKT signaling pathways. Accordingly it has been hypothesized that pretreatment of HPC-MSC(s) with apelin 13 would be an effective approach to modify and possibly enhance the efficacy of MSCs in cell therapy of diabetes.