Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis

• Material Type: 博士論文
• Title: Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis
• Author/Editor: 村上, 俊介
• Author Heading: 村上, 俊介
• Publication, Distribution, etc.: The Japanese Society for Regenerative Medicine
• Publication Date: 2023-03-20
• Publication Date (W3CDTF): 2023-03-20
• Alternative Title: 低分子化合物を用いた肝前駆細胞による非アルコール性脂肪性肝炎の改善
• Degree grantor/type: Nagasaki University (長崎大学)
• Date Granted: 2023-03-20
• Date Granted (W3CDTF): 2023-03-20
• Dissertation Number: 甲医歯薬第1508号
• Degree Type: 博士(医学)
• Text Language Code: eng
• Subject Heading: Liver progenitor cells; Cell transplantation; Chemically induced; Hepatic fibrosis; Hepatocytes
• Target Audience: 一般
• Note (General): Background Can Background be changed from bold to normal text?: Chemically-induced liver progenitors (CLiPs) have promising applications in liver regenerative medicine. We aimed to clarify the efficacy of CLiPs for ameliorating fibrosis in a diet-induced nonalcoholic steatohepatitis rat model, since nonalcoholic fatty liver disease is currently recognized as the most common form of chronic liver disease in developed countries. Methods: Primary mature hepatocytes were isolated from 7-week-old male Wistar rats. To establish CLiPs, isolated hepatocytes were cultured in differentiation medium composed of Y-27632, A-83-01, and CHIR99021 (YAC medium). As an animal model that reproduces NASH pathophysiology, 6-week-old severe combined immunodeficient (SCID) mice were carefully selected and prepared and fed with choline-deficient, L-amino acid-defined, high-fat diet (HFD). After 12 weeks’ HFD feeding, the mice were assigned to continue HFD with or without the administration of rat CLiPs (HFD þ CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semiquantitatively evaluated according to histology. Liver parenchyma and blood samples were collected for biochemical analyses. Results: Rat CLiPs were positive for CK19 and EpCAM were successfully delivered to the liver. At 8 weeks after CLiPs transplantation, the HFD þ CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD þ CLiPs group, as demonstrated by Azan staining and aSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD þ CLiPs group. Conclusions: The antifibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.; 長崎大学学位論文 学位記番号:博(医歯薬)甲第1508号 学位授与年月日:令和5年3月20日; Author: Shunsuke Murakami, Akihiko Soyama, Daisuke Miyamoto, Takanobu Hara, Kunihito Matsuguma, Hajime Imamura, Hajime Matsushima, Takayuki Tanaka, Yasuhiro Maruya, Tomohiko Adachi, Satoshi Miuma, Masaaki Hidaka, Kengo Kanetaka, Takahiro Ochiya, Susumu Eguchi; Citation: Regenerative Therapy, 21, pp. 574-583; 2022; identifier:Nagasaki University (長崎大学), 博士(医学) (2023-03-20); http://hdl.handle.net/10069/00042241
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• Date Accepted (W3CDTF): 2023-05-05T22:12:35+09:00
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• Periodical Title (URI): http://hdl.handle.net/10069/00042337
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