Melatonin preconditioning of bone marrow-derived mesenchymal stem cells promotes their engraftment and improves renal regeneration in a rat model of chronic kidney disease

Bone marrow-derived mesenchymal stem cells (BMMSCs) transplantation has shown to be effective in treating chronic kidney disease. However, the effectiveness of this strategy is constrained by low homing and survival rate of transplanted cells in the injured organs. Therefore, developing strategies to improve homing and cell survival rate and therapeutic potential in cell-based therapies seems necessary. The purpose of this study is to evaluate the effect of pretreating BMMSCs with melatonin (MT) on the prosurvival and renoprotective of transplanted cells into the irreversible model of unilateral ureteral obstruction. Adult male Sprague-Dawley rats were randomized into four groups: Sham, UUO, UUO+BMMSCs, and UUO+BMMSCs+MT. The results of our study demonstrated that preconditioning with MT enhanced homing of BMMSCs into the injured kidney. MT reduced the number of TUNEL positive transplanted cells in the UUO+BMMSCs+MT group. The UUO+BMMSCs+MT group showed lower expressions of TGF-1, -SMA and TNF- at both gene and protein levels but higher expression of E-cadherin compared with the UUO+BMMSCs group. In addition, MT preconditioned BMMSCs ameliorated basement membrane disruption and histological status of injured renal tubules and also reduced fibrosis in damaged kidneys. In conclusion, our results show that stem cells pretreated by MT may represent a feasible approach for improving the beneficial effects of stem cell therapy and significantly enhance their survival after transplantation to the injured kidney.