Bone marrow derived-mesenchymal stem cell improves diabetes-associated fatty liver via mitochondria transformation in mice

Youkun Bi,Yanyun Wu,Keqi Zhu,Chentao Shi,Guangju Ji,Zhiguang Yang,Mengqi Zhang,Baoqi Fan,Xuejun Guo

doi:10.1186/s13287-021-02663-5

Abstract

BackgroundNon-alcoholic fatty liver disease (NAFLD) has become a global epidemic disease. Its incidence is associated with type 2 diabetes mellitus (T2DM). Presently, there is no approved pharmacological agents specially developed for NAFLD. One promising disease-modifying strategy is the transplantation of stem cells to promote metabolic regulation and repair of injury.MethodIn this study, a T2DM model was established through 28-week high-fat diet (HFD) feeding resulting in T2DM-associated NAFLD, followed by the injection of bone marrow mesenchymal stem cells (BMSCs). The morphology, function, and transfer of hepatocyte mitochondria were evaluated in both vivo and in vitro.ResultsBMSC implantation resulted in the considerable recovery of increasing weight, HFD-induced steatosis, liver function, and disordered glucose and lipid metabolism. The treatment with BMSC transplantation was accompanied by reduced fat accumulation. Moreover, mitochondrial transfer was observed in both vivo and vitro studies. And the mitochondria-recipient steatotic cells exhibited significantly enhanced OXPHOS activity, ATP production, and mitochondrial membrane potential, and reduced reactive oxygen species levels, which were not achieved by the blocking of mitochondrial transfer.ConclusionMitochondrial transfer from BMSCs is a feasible process to combat NAFLD via rescuing dysfunction mitochondria, and has a promising therapeutic effect on metabolism-related diseases.

Highlights

The global prevalence of non-alcoholic fatty liver disease (NAFLD) has significantly increased in parallel with obesity [1]
bone marrow mesenchymal stem cell (BMSC) implantation resulted in the considerable recovery of increasing weight, high-fat diet (HFD)-induced steatosis, liver function, and disordered glucose and lipid metabolism
The mitochondria-recipient steatotic cells exhibited significantly enhanced OXPHOS activity, ATP production, and mitochondrial membrane potential, and reduced reactive oxygen species levels, which were not achieved by the blocking of mitochondrial transfer

Summary

Introduction

The global prevalence of non-alcoholic fatty liver disease (NAFLD) has significantly increased in parallel with obesity [1]. NAFLD is characterized by diffuse fatty infiltration, accompanied by non-alcoholic steatohepatitis (NASH), and hepatic fibrosis [2]. The metabolic disorder of triglycerides and cholesterol results in the accumulation of massive lipid droplets in hepatocytes and subsequent hepatic steatosis, facilitating the follow-up of insulin resistance [3, 4]. Many studies have reported a strong association between NAFLD and type 2 diabetes mellitus (T2DM), as over 70% of T2DM. Non-alcoholic fatty liver disease (NAFLD) has become a global epidemic disease. Its incidence is associated with type 2 diabetes mellitus (T2DM). One promising disease-modifying strategy is the transplantation of stem cells to promote metabolic regulation and repair of injury

Methods

Results

Discussion

Conclusion