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

• Material Type: 博士論文
• Title: Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles
• Author/Editor: Watanabe, Takayuki
• Publication Date: 2020-09-23
• Publication Date (W3CDTF): 2020-09-23
• Alternative Title: 線維化を伴う非アルコール性脂肪性肝炎のモデルマウスの開発、および間葉系幹細胞とその細胞分泌小胞を投与した際の治療効果の検証
• Degree grantor/type: 新潟大学
• Date Granted: 2020-09-23
• Date Granted (W3CDTF): 2020-09-23
• Dissertation Number: 甲第4788号
• Degree Type: 博士(医学)
• Conferring No. (Dissertation): 甲第4788号
• Text Language Code: eng
• Note (General): 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.; Regenerative Therapy. 2020, 14, 252-261.; 新大院博(医)甲第958号; 元資料の権利情報 : 【○!C】 2020, The Japanese Society for Regenerative Medicine. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
• DOI: info:doi/10.1016/j.reth.2020.03.012; https://doi.org/info:doi/10.1016/j.reth.2020.03.012
• Persistent ID (NDL): info:ndljp/pid/11583371; https://dl.ndl.go.jp/pid/11583371
• Collection: 障害者向け資料
• Collection (Materials For Handicapped People:1): テキストデータ
• Collection (particular): 国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文; https://dl.ndl.go.jp/collections/A00014
• Acquisition Basis: 博士論文（自動収集）
• Date Accepted (W3CDTF): 2020-12-08T06:37:43+09:00
• Date Created (W3CDTF): 2020-11-12
• Format (IMT): application/pdf
• Access Restrictions: 国立国会図書館内限定公開
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• Periodical Title (URI): http://hdl.handle.net/10191/00051949
• Data Provider (Database): 国立国会図書館 : 国立国会図書館デジタルコレクション; https://dl.ndl.go.jp