Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis
Abstract Accumulating evidence has shown that adipose-derived stem cells (ADSCs) have the potential to differentiate into hepatic lineages, which are ideal engraftments for tissue-engineered repair. In this study, we investigated the potential of transplanted induced hepatocyte-like cells (iHEPs) in...
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Nature Portfolio
2024-11-01
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Online Access: | https://doi.org/10.1038/s41598-024-77555-8 |
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author | Hui Liu Xiaojuan Bi Ning Yang Xue Zhang Bingbing Fang Nuerbaiti Kusuman Wenmei Ma Jing Li Jin Chu Li Sun Liang Li Guodong Lü Renyong Lin |
author_facet | Hui Liu Xiaojuan Bi Ning Yang Xue Zhang Bingbing Fang Nuerbaiti Kusuman Wenmei Ma Jing Li Jin Chu Li Sun Liang Li Guodong Lü Renyong Lin |
author_sort | Hui Liu |
collection | DOAJ |
description | Abstract Accumulating evidence has shown that adipose-derived stem cells (ADSCs) have the potential to differentiate into hepatic lineages, which are ideal engraftments for tissue-engineered repair. In this study, we investigated the potential of transplanted induced hepatocyte-like cells (iHEPs) in treating hepatic alveolar echinococcosis and describe an efficient three-step protocol for the generation of iHEPs in vitro from ADSCs. The expression of hepatocyte lineage markers was assessed and iHEPs function was evaluated by Periodic acid-Schiff staining. iHEPs were intravenously transplanted into mice infected with Echinococcus multilocularis. Histopathological analysis and liver function tests were used to assess therapeutic effects. The iHEPs exhibit morphological features and a glycogen storage function similar to those of mature hepatocytes and demonstrate an upregulation in hepatic gene programs with increasing induction time. Following transplantation, iHEPs were observed surrounding the metacestode lesions in the liver parenchyma of E. multilocularis-infected mice. iHEPs transplantation effectively restored liver function and improved liver injury in the infected mice. Additionally, we observed significant activation of the Wnt/β-catenin signaling pathway in the livers of infected mice transplanted with iHEPs. Our results provide evidence that iHEPs transplantation can alleviate E. multilocularis-induced liver injury, potentially creating new avenues for treating liver injury in end-stage hepatic alveolar echinococcosis. |
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id | doaj-art-27517f06079e4ba293f949041513bf57 |
institution | Kabale University |
issn | 2045-2322 |
language | English |
publishDate | 2024-11-01 |
publisher | Nature Portfolio |
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spelling | doaj-art-27517f06079e4ba293f949041513bf572025-02-09T12:38:13ZengNature PortfolioScientific Reports2045-23222024-11-0114111310.1038/s41598-024-77555-8Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus MultilocularisHui Liu0Xiaojuan Bi1Ning Yang2Xue Zhang3Bingbing Fang4Nuerbaiti Kusuman5Wenmei Ma6Jing Li7Jin Chu8Li Sun9Liang Li10Guodong Lü11Renyong Lin12State Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityPathology department, The First Affiliated Hospital of Xinjiang Medical UniversityCollege of Pharmacy, Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityState Key Laboratory of Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asia, Clinical Medical Research Institute, The First Affiliated Hospital of Xinjiang Medical UniversityAbstract Accumulating evidence has shown that adipose-derived stem cells (ADSCs) have the potential to differentiate into hepatic lineages, which are ideal engraftments for tissue-engineered repair. In this study, we investigated the potential of transplanted induced hepatocyte-like cells (iHEPs) in treating hepatic alveolar echinococcosis and describe an efficient three-step protocol for the generation of iHEPs in vitro from ADSCs. The expression of hepatocyte lineage markers was assessed and iHEPs function was evaluated by Periodic acid-Schiff staining. iHEPs were intravenously transplanted into mice infected with Echinococcus multilocularis. Histopathological analysis and liver function tests were used to assess therapeutic effects. The iHEPs exhibit morphological features and a glycogen storage function similar to those of mature hepatocytes and demonstrate an upregulation in hepatic gene programs with increasing induction time. Following transplantation, iHEPs were observed surrounding the metacestode lesions in the liver parenchyma of E. multilocularis-infected mice. iHEPs transplantation effectively restored liver function and improved liver injury in the infected mice. Additionally, we observed significant activation of the Wnt/β-catenin signaling pathway in the livers of infected mice transplanted with iHEPs. Our results provide evidence that iHEPs transplantation can alleviate E. multilocularis-induced liver injury, potentially creating new avenues for treating liver injury in end-stage hepatic alveolar echinococcosis.https://doi.org/10.1038/s41598-024-77555-8Hepatocyte-like cellsAdipose-derived stem cellsEchinococcus multilocularisLiver injury |
spellingShingle | Hui Liu Xiaojuan Bi Ning Yang Xue Zhang Bingbing Fang Nuerbaiti Kusuman Wenmei Ma Jing Li Jin Chu Li Sun Liang Li Guodong Lü Renyong Lin Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis Scientific Reports Hepatocyte-like cells Adipose-derived stem cells Echinococcus multilocularis Liver injury |
title | Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis |
title_full | Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis |
title_fullStr | Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis |
title_full_unstemmed | Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis |
title_short | Induced hepatocyte-like cells derived from adipose-derived stem cells alleviates liver injury in mice infected with Echinococcus Multilocularis |
title_sort | induced hepatocyte like cells derived from adipose derived stem cells alleviates liver injury in mice infected with echinococcus multilocularis |
topic | Hepatocyte-like cells Adipose-derived stem cells Echinococcus multilocularis Liver injury |
url | https://doi.org/10.1038/s41598-024-77555-8 |
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