Overexpression of CCR2 in mesenchymal stem cells contributes to homing and liver regeneration

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 therapy. The purpose of this study was to clarify the effects of chemokine CCL2 and its receptor CCR2 on homing of bone mesenchymal stem cells (BMSCs) after partial hepatectomy and the mechanism by which they enhance liver regeneration. 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 bone marrow MSCs (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 a liver index, HE staining and serum ALT and AST contents. The migration ability of BMSCs modified by CCR2 was observed by a transwell test and PKH26 staining. The influence of CCL2-CCR2 on the homing signalling pathway of BMSCs was detected by western blot and scratch experiments. It was found that CCL2 expression was up-regulated during the whole process of liver regeneration. BMSCs could express the CCR2 receptor, but lentivirus-transfected BMSCs could express more CCR2. The BMSCs modified by CCR2 showed strong migration ability. At 72 h after partial hepatectomy, compared with KM-BMSCs group, the liver index of the KM-BMSCs-CCR2 group was higher, the liver tissue structure was more normal, and the levels of ALT and AST were lower. Expression of the Rho/ROCK signalling pathway proteins increased in the liver of the KM-BMSCs-CCR2 group, while migration ability of BMSCs decreased after treatment with the ROCK inhibitor Y-27632. In summary, this study suggested that the expression of CCR2 on BMSCs enhanced their targeted migration to the liver of partially hepatectomized mice and promoted liver regeneration. The Rho/ROCK signalling pathway plays an important role in the homing of BMSCs.