Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles

• DOI: 10.1016/j.reth.2020.03.012
• Publication Date: 2020-05-16T00:30:02Z
• Authors: Takayuki Watanabe; Atsunori Tsuchiya; Suguru Takeuchi; Shunsuke Nojiri; Tomoaki Yoshida; Masahiro Ogawa; Michiko Itoh; Masaaki Takamura; Takayoshi Suganami; Yoshihiro Ogawa; Shuji Terai
• Keywords: Steatohepatitis

Currently, there are no approved drugs for treating non-alcoholic steatohepatitis (NASH); however, mesenchymal stem cells (MSCs) and their small extracellular vesicles (sEVs), which possess immunomodulatory activities, potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation fibrosis using the pre-established melanocortin type-4 receptor knockout (Mc4r-KO) lipopolysaccharide (LPS), evaluate therapeutic effect MSCs sEVs.Mc4r-KO mice (8 weeks old, male) were fed western diet (WD) 8 weeks. Next, intraperitoneally injected (LPS) twice week 4 while continuing WD. To confirm sEVs, human adipose tissue-derived or sEVs administered 12 after initiation WD, serum testing, quantitative analysis fibrosis, reverse transcription-polymerase chain reaction qRT-PCR performed.By providing WD combined LPS treatment, we successfully developed fibrosis. Both decreased alanine transaminase levels inflammatory markers based on qRT-PCR. Histological showed that MSC sEV treatment did not affect fat accumulation. However, an improvement in groups treated was observed. Furthermore, administering significant increase anti-inflammatory macrophages liver.We confirmed anti-fibrotic effects may be options future therapy.