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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Main Authors: 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
Format: Article
Language:English
Published: Nature Portfolio 2024-11-01
Series:Scientific Reports
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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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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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