Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles
| العنوان: | Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles |
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| المؤلفون: | Takayoshi Suganami, Shuji Terai, Shunsuke Nojiri, Masahiro Ogawa, Tomoaki Yoshida, Atsunori Tsuchiya, Suguru Takeuchi, Takayuki Watanabe, Yoshihiro Ogawa, Masaaki Takamura, Michiko Itoh |
| المصدر: | Regenerative Therapy Regenerative Therapy, Vol 14, Iss, Pp 252-261 (2020) |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | 0301 basic medicine, NAFLD, non-alcoholic fatty liver disease, Cirrhosis, MC4R, melanocortin-4 receptor-deficient, Lipopolysaccharide, ALT, alanine transaminase, NASH, non-alcoholic steatohepatitis, Biomedical Engineering, Adipose tissue, MSC, mesenchymal stem cell, Small extracellular vesicles, Pharmacology, hCLS, hepatic crown-like structure, Biomaterials, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, MCD, methionine-choline-deficient diet, Fibrosis, sEV, small extracellular vesicle, medicine, lcsh:QH573-671, Receptor, Non-alcoholic steatohepatitis, lcsh:R5-920, WD, Western diet, biology, business.industry, lcsh:Cytology, ND, normal diet, Mesenchymal stem cell, medicine.disease, 030104 developmental biology, chemistry, Alanine transaminase, biology.protein, Mesenchymal stem cells, Original Article, Steatohepatitis, business, lcsh:Medicine (General), HCC, hepatocellular carcinoma, T-bil, total bilirubin, T-cho, total cholesterol, 030217 neurology & neurosurgery, Developmental Biology |
| الوصف: | Introduction 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, are potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation of fibrosis using the pre-established melanocortin type-4 receptor knockout (Mc4r-KO) NASH mouse model and lipopolysaccharide (LPS), and to evaluate the therapeutic effect of MSCs and their sEVs. Methods Mc4r-KO mice (8 weeks old, male) were fed a western diet (WD) for 8 weeks. Next, the mice were intraperitoneally injected with lipopolysaccharide (LPS) twice a week for 4 weeks while continuing the WD. To confirm the therapeutic effect of MSCs and sEVs, human adipose tissue-derived MSCs or their sEVs were administered 12 weeks after initiation of the WD, and serum testing, quantitative analysis of fibrosis, and quantitative reverse transcription-polymerase chain reaction qRT-PCR were performed. Results By providing a WD combined with LPS treatment, we successfully developed a NASH model with rapid accumulation of fibrosis. Both human MSCs and their sEVs decreased serum alanine transaminase levels and inflammatory markers based on qRT-PCR. Histological analysis showed that MSC or sEV treatment did not affect fat accumulation. However, an improvement in fibrosis in the groups treated with MSCs and their sEVs was observed. Furthermore, after administering MSCs and sEVs, there was a significant increase in anti-inflammatory macrophages in the liver. Conclusion We successfully developed a NASH model with rapid accumulation of fibrosis and confirmed the anti-inflammatory and anti-fibrotic effects of MSCs and their sEVs, which may be options for future therapy. Graphical abstract Image 1 Highlights • A new animal model of NASH that resembles the human disease was developed. • The new model showed characteristic pathological features of NASH. • Treatment with MSCs and MSC-derived sEVs lowered fibrosis in the animal model. • MSCs and MSC-derived sEVs may be developed as potential therapeutics for NASH. |
| تدمد: | 2352-3204 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03c605b87d1574bec9c086c0f3c9517bTest https://pubmed.ncbi.nlm.nih.gov/32455155Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....03c605b87d1574bec9c086c0f3c9517b |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 23523204 |
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