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

摘要

Abstract 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 6 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.