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Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles
http://hdl.handle.net/10191/00051949
http://hdl.handle.net/10191/00051949060eac38-943d-4e43-9e89-0be779670d8c
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本文 (4.1 MB)
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| Item type | 学位論文 / Thesis or Dissertation(1) | |||||
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| 公開日 | 2020-11-12 | |||||
| タイトル | ||||||
| タイトル | Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Non-alcoholic steatohepatitis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Cirrhosis | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Mesenchymal stem cells | |||||
| キーワード | ||||||
| 主題Scheme | Other | |||||
| 主題 | Small extracellular vesicles | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_46ec | |||||
| 資源タイプ | thesis | |||||
| その他のタイトル | ||||||
| その他のタイトル | 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 | |||||
| 著者 |
Watanabe, Takayuki
× Watanabe, Takayuki |
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| 著者別名 | ||||||
| 識別子Scheme | WEKO | |||||
| 識別子 | 178205 | |||||
| 姓名 | 渡邉, 貴之 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 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. | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | Regenerative Therapy. 2020, 14, 252-261. | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | info:doi/10.1016/j.reth.2020.03.012 | |||||
| 権利 | ||||||
| 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/). | |||||
| 著者版フラグ | ||||||
| 値 | ETD | |||||
| 学位名 | ||||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関名 | 新潟大学 | |||||
| 学位授与年月日 | ||||||
| 学位授与年月日 | 2020-09-23 | |||||
| 学位授与番号 | ||||||
| 学位授与番号 | 13101甲第4788号 | |||||
| 学位記番号 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 新大院博(医)甲第958号 | |||||
