Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis
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...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352320422001079 |
| _version_ | 1811201986153938944 |
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| 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 |
| author_facet | 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 |
| author_sort | Shunsuke Murakami |
| collection | DOAJ |
| description | 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 + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively 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 + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans. |
| first_indexed | 2024-04-12T02:31:07Z |
| format | Article |
| id | doaj.art-9de2071400af4b3b93ea0bc6057d0736 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2024-04-12T02:31:07Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-9de2071400af4b3b93ea0bc6057d07362022-12-22T03:51:46ZengElsevierRegenerative Therapy2352-32042022-12-0121574583Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitisShunsuke Murakami0Akihiko Soyama1Daisuke Miyamoto2Takanobu Hara3Kunihito Matsuguma4Hajime Imamura5Hajime Matsushima6Takayuki Tanaka7Yasuhiro Maruya8Tomohiko Adachi9Satoshi Miuma10Masaaki Hidaka11Kengo Kanetaka12Takahiro Ochiya13Susumu Eguchi14Department of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Gastroenterology and Hepatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, JapanDepartment of Molecular and Cellular Medicine, Tokyo Medical University, Tokyo, JapanDepartment of Surgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Corresponding author. Nagasaki University Graduate School of Biomedical Sciences, 1-7-1, Sakamoto, 852-8501, Nagasaki, Japan (Fax: +81-95-819-7319).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 + CLiPs and HFD-CLiPs, respectively). Rat CLiPs were administered from the spleen. Hepatic fibrosis was semi-quantitatively 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 + CLiPs group showed significantly less positive staining than the HFD-CLiPs group. Alanine aminotransferase significantly improved in the HFD + CLiPs group, as demonstrated by Azan staining and αSMA immunostaining. RT qPCR showed that the liver expression of MMP2 and 9 tended to be higher in the HFD + CLiPs group. Conclusions: The anti-fibrotic effect of CLiPs was demonstrated in the immunodeficient NASH animal model and may have therapeutic applications in humans.http://www.sciencedirect.com/science/article/pii/S2352320422001079Liver progenitor cellsCell transplantationChemically inducedHepatic fibrosisHepatocytes |
| spellingShingle | 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 Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis Regenerative Therapy Liver progenitor cells Cell transplantation Chemically induced Hepatic fibrosis Hepatocytes |
| title | Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis |
| title_full | Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis |
| title_fullStr | Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis |
| title_full_unstemmed | Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis |
| title_short | Transplantation of chemically-induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet-induced nonalcoholic steatohepatitis |
| title_sort | transplantation of chemically induced liver progenitor cells ameliorates hepatic fibrosis in mice with diet induced nonalcoholic steatohepatitis |
| topic | Liver progenitor cells Cell transplantation Chemically induced Hepatic fibrosis Hepatocytes |
| url | http://www.sciencedirect.com/science/article/pii/S2352320422001079 |
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