Abstract
BackgroundTransplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). However, the homing efficiency of BMSCs to the injured liver sites appears to be poor. In this study, we aimed to determine if overexpression of c-Met in BMSCs could promote the homing ability of BMSCs to rat livers affected by ALF.MethodsOverexpression of c-Met in BMSCs (c-Met-BMSCs) was attained by transfection of naive BMSCs with the lenti-c-Met-GFP. The impact of transplanted c-Met-BMSCs on both homing and repair of ALF was evaluated and compared with lenti-GFP empty vector transfected BMSCs (control BMSCs).ResultsAfter cells were transfected with the lenti-c-Met-GFP vector, the BMSCs displayed very high expression of c-Met protein as demonstrated by Western blot. In addition, in vitro transwell migration assays showed that the migration ability of c-Met-BMSCs was significantly increased in comparison with that of control BMSCs (P < 0.05), and was dependent on hepatocyte growth factor (HGF). Furthermore, rats with ALF that received transplanted c-Met-BMSCs showed significantly improved homing ability to the injured liver; this was accompanied by elevated survival rates and liver function in the ALF rats. Parallel pathological examination further confirmed that transplantation of c-Met-BMSCs ameliorated liver injury with reduced hepatic activity index (HAI) scores, and that the effects of c-Met-BMSCs were more profound than those of control BMSCs.ConclusionsOverexpression of c-Met promotes the homing of BMSCs to injured hepatic sites in a rat model of ALF, thereby improving the efficacy of BMSC therapy for ALF repair.
Highlights
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF)
Preparation and characterization of BMSCs and c-MetBMSCs Seven to ten days after isolated BMSCs were cultured the cell morphology was examined under an inverted microscope
Monolayers of BMSCs were formed with cells displaying a spindle shape and arranged in radial concentric circles or with broom-like growth
Summary
Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) has emerged as a novel therapy for acute liver failure (ALF). The homing efficiency of BMSCs to the injured liver sites appears to be poor. Wang et al Stem Cell Research & Therapy (2017) 8:162 they have been employed for the repair of damaged tissues or organs including the liver. BMSCs have been shown to be effective in the treatment of hepatic cirrhosis and liver failure. The ability of BMSCs to home to the injured liver has been reported as being poor. This has posed challenges for development of their application [4]. Given the significant morbidity and mortality associated with ALF, there is an urgent need to enhance the homing capabilities of BMSCs in order to improve the efficacy of these potent cell types
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