The efficacy of cell therapy for many diseases can be limited by the poor survival of implanted cells in an environment of tissue injury. Melatonin has been reported to have anti-oxidative and anti-apoptotic effects. Adipose tissue-derived mesenchymal stromal cells (ASCs), cells easily obtained in high amounts and with minimal discomfort, have shown great promise in cell therapy applications, such as in acute kidney injury. We hypothesized that melatonin pre-treatment of human ASCs (hASCs) would improve their renoprotective and pro-survival effects. We therefore investigated the action of melatonin on hASCs, as well as the effect of the resulting hASCs conditioned media (CM) on human kidney cells exposed to oxidative and apoptotic injury-provoking doses of cisplatin. Our results demonstrated that pre-treatment of hASCs with melatonin, 100μM for 3 hours, significantly increased their proliferation and their expression of pro-survival P-Erk1/2 and P-Akt, and of anti-oxidative enzymes catalase and heme oxygenase (HO)-1. In addition, the CM from hASCs pre-treated with melatonin provoked a significantly higher proliferation and migration of HK-2 human kidney epithelial cells. Furthermore, this CM exerted significantly higher pro-survival and anti-apoptotic actions on HK-2 cells exposed to cisplatin in vitro. Western blot analysis showed higher expression of P-Erk1/2, Bcl-2, superoxide dismutase-1 (SOD-1) and HO-1 in the HK-2 cells exposed to cisplatin in the presence of CM from melatonin-pre-treated hASCs. In sum, our study revealed that in vitro pre-treatment of hASCs with melatonin may significantly enhance their survival and their therapeutic effectiveness on injured tissue.
- kidney cells
- mesenchymal stromal cells
- adipose tissue
- stem cells
- Copyright © 2014, American Journal of Physiology - Renal Physiology