CCR2 Contributes to the Homing of MSCs and Liver Regeneration

Abstract Objective: Mesenchymal stem cells (MSCs) are emerging as a new therapeutic strategy for liver diseases.However, the inability of stem cells to efficiently return to the target tissue is a major obstacle to repair.The chemokine family and its receptors play an important role in the homing of mesenchymal stem cells.This study was conducted to verify that the overexpression of chemokine receptor CCR2 can contribute to the homing of MSCs, improve the therapeutic effect, and clarify the mechanism of action.Methods: A mouse model of partial hepatectomy was established. Transcriptome sequencing was used to detect the expression of CCl2 in liver tissue.CCR2 was transfected with lentivirus into BMSCs, and the expression of CCR2 in BMSCs was detected by qRT-PCR. The effect of BMSCs overexpressing CCR2 on liver regeneration in mice with partial hepatectomy was detected by liver index, HE staining and serum ALT and AST content. The migration ability of BMSCs modified by CCR2 was observed by Transwell test and PKH26 staining. The influence of CCl2-CCR2 on the homing signaling pathway of BMSCs was detected by Western blot and scratch experiments.Results: The expression of CCl2 was up-regulated during the whole process of liver regeneration.BMSCs can express CCR2 receptor, but lentivirus transfected BMSCs can express more CCR2.The BMSCs modified by CCR2 showed stronger migration ability. At 72 hours after partial hepatectomy, the liver index of BMSCS-CCR2 group was higher than that of BMSCs group, the liver tissue structure tended to be normal, and ALT and AST content decreased significantly. Expression of Rho/ROCK signaling pathway protein was increased in the liver of BMSCS-CCR2 group, while cell migration was decreased after treatment with the ROCK inhibitor Y-27632.Conclusion: In summary, this study suggests that CCR2 expression on BMSCs enhances their targeted migration to the liver of partial hepatectomy mice and promotes liver regeneration. The Rho/ROCK signaling pathway plays an important role in the homing of BMSCs.