Resveratrol pretreatment enhanced homing of SDF-1α-preconditioned bone marrow-derived mesenchymal stem cells in a rat model of liver cirrhosis.

Stromal cell-derived factor-1α (SDF-1α) has been known to implicate in homing of MSCs, and resveratrol has been reported to have a positive influence on SDF-1 level in the site of injury. In this study, a combined strategy was applied to evaluate bone marrow-derived MSCs (BMSCs) homing to the rat model of liver cirrhosis induced by common bile duct ligation (CBDL): (1) pretreatment delivery of resveratrol into the cirrhotic liver, and (2) transplantation of ex vivo BMSC preconditioning with SDF-1α. BMSCs were preconditioned with 10 ng/µL SDF-1α for 1 h and then labeled with the CM-Dil. Cirrhosis was induced by CBDL. Animals received intraperitoneal injection of resveratrol for 7 days, started on day 28 of CBDL post-operative. On day 36 post-operative, 1 × 10 of SDF-1α-preconditioned BMSCs was injected via caudal vein. Animals were sacrificed at 72 h post-cell transplantation. Immunofluorescence and flow cytometry assessments showed that the BMSC+SDF+RV group had an increased rate of homing into the liver, but it had a decreased rate of homing into the lung and spleen, as compared with the other groups (P < 0.05). The BMSC+SDF+RV group showed high protein expression of SIRT1, but low protein expression of p53 in the liver (P < 0.05 vs other groups). CXCR4 and matrix metalloproteinase (MMP)-9 highly expressed in SDF-1α-preconditioned BMSCs in vitro, and that AKTs and CXCL12 expressed in injured liver undergoing resveratrol injection. Our findings suggest that reseveratrol pretreatment prior to SDF-1α preconditioning could be a promising strategy for designing cell-based therapies for liver cirrhosis.