Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells
Background:. Cell therapy demonstrates promising potential as a substitute therapeutic approach for liver cirrhosis. We have developed a strategy to effectively expand murine and human hepatocyte-derived liver progenitor-like cells (HepLPCs) in vitro. The primary objective of the present study was t...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wolters Kluwer Health/LWW
2025-02-01
|
| Series: | Hepatology Communications |
| Online Access: | http://journals.lww.com/10.1097/HC9.0000000000000614 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832540468696580096 |
|---|---|
| author | Xu Zhou Wen-Ming Liu Han-Yong Sun Yuan Peng Ren-Jie Huang Cai-Yang Chen Hong-Dan Zhang Shen-Ao Zhou Hong-Ping Wu Dan Tang Wei-Jian Huang Han Wu Qi-Gen Li Bo Zhai Qiang Xia Wei-Feng Yu He-Xin Yan |
| author_facet | Xu Zhou Wen-Ming Liu Han-Yong Sun Yuan Peng Ren-Jie Huang Cai-Yang Chen Hong-Dan Zhang Shen-Ao Zhou Hong-Ping Wu Dan Tang Wei-Jian Huang Han Wu Qi-Gen Li Bo Zhai Qiang Xia Wei-Feng Yu He-Xin Yan |
| author_sort | Xu Zhou |
| collection | DOAJ |
| description | Background:. Cell therapy demonstrates promising potential as a substitute therapeutic approach for liver cirrhosis. We have developed a strategy to effectively expand murine and human hepatocyte-derived liver progenitor-like cells (HepLPCs) in vitro. The primary objective of the present study was to apply HepLPCs to the treatment of liver cirrhosis and to elucidate the underlying mechanisms responsible for their therapeutic efficacy.
Methods:. The effects of allogeneic or xenogeneic HepLPC transplantation were investigated in rat model of liver cirrhosis. Liver tissues were collected and subjected to immunostaining to assess changes in histology. In vitro experiments used HSCs to explore the antifibrotic properties of HepLPC-secretomes and their underlying molecular mechanisms. Additionally, proteomic analysis was conducted to characterize the protein composition of HepLPC-secretomes.
Results:. Transplantation of HepLPCs resulted in decreased active fibrogenesis and net fibrosis in cirrhosis models. Apoptosis of HSCs was observed in vivo after HepLPC treatment. HepLPC-secretomes exhibited potent inhibition of TGF-β1-induced HSC activation and promoted apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways in vitro. Furthermore, synergistic effects between amphiregulin and FGF19 within HepLPC-secretomes were identified, contributing to HSC apoptosis and exerting antifibrotic effects via activation of the janus kinase-STAT1 pathway.
Conclusions:. HepLPCs have the potential to ameliorate liver cirrhosis by inducing STAT1-dependent apoptosis in HSCs. Amphiregulin and FGF19 are key factors responsible for STAT1 activation, representing promising novel therapeutic targets for the treatment of liver cirrhosis. |
| format | Article |
| id | doaj-art-7d2b0c131d0b4f0f8a2f19cff15d42a2 |
| institution | Kabale University |
| issn | 2471-254X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wolters Kluwer Health/LWW |
| record_format | Article |
| series | Hepatology Communications |
| spelling | doaj-art-7d2b0c131d0b4f0f8a2f19cff15d42a22025-02-05T02:10:59ZengWolters Kluwer Health/LWWHepatology Communications2471-254X2025-02-019210.1097/HC9.0000000000000614HC90000000000000614Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cellsXu Zhou0Wen-Ming Liu1Han-Yong Sun2Yuan Peng3Ren-Jie Huang4Cai-Yang Chen5Hong-Dan Zhang6Shen-Ao Zhou7Hong-Ping Wu8Dan Tang9Wei-Jian Huang10Han Wu11Qi-Gen Li12Bo Zhai13Qiang Xia14Wei-Feng Yu15He-Xin Yan16 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 5 Department of Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 6 Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 Shanghai Celliver Biotechnology Co. Ltd., Shanghai, China 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 2 Shanghai Celliver Biotechnology Co. Ltd., Shanghai, China 2 Shanghai Celliver Biotechnology Co. Ltd., Shanghai, China 7 Molecular Epidemiology Laboratory, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai, China 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 8 Hubei Key Laboratory of Tumour Biological Behaviors, Department of Radiation and Medical Oncology, Zhongnan Hospital of Wuhan University, Wuhan, China 5 Department of Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 6 Department of Interventional Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 5 Department of Hepatic Surgery, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China 1 Department of Anesthesiology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, ChinaBackground:. Cell therapy demonstrates promising potential as a substitute therapeutic approach for liver cirrhosis. We have developed a strategy to effectively expand murine and human hepatocyte-derived liver progenitor-like cells (HepLPCs) in vitro. The primary objective of the present study was to apply HepLPCs to the treatment of liver cirrhosis and to elucidate the underlying mechanisms responsible for their therapeutic efficacy. Methods:. The effects of allogeneic or xenogeneic HepLPC transplantation were investigated in rat model of liver cirrhosis. Liver tissues were collected and subjected to immunostaining to assess changes in histology. In vitro experiments used HSCs to explore the antifibrotic properties of HepLPC-secretomes and their underlying molecular mechanisms. Additionally, proteomic analysis was conducted to characterize the protein composition of HepLPC-secretomes. Results:. Transplantation of HepLPCs resulted in decreased active fibrogenesis and net fibrosis in cirrhosis models. Apoptosis of HSCs was observed in vivo after HepLPC treatment. HepLPC-secretomes exhibited potent inhibition of TGF-β1-induced HSC activation and promoted apoptosis through signal transducer and activator of transcription (STAT)1-mediated pathways in vitro. Furthermore, synergistic effects between amphiregulin and FGF19 within HepLPC-secretomes were identified, contributing to HSC apoptosis and exerting antifibrotic effects via activation of the janus kinase-STAT1 pathway. Conclusions:. HepLPCs have the potential to ameliorate liver cirrhosis by inducing STAT1-dependent apoptosis in HSCs. Amphiregulin and FGF19 are key factors responsible for STAT1 activation, representing promising novel therapeutic targets for the treatment of liver cirrhosis.http://journals.lww.com/10.1097/HC9.0000000000000614 |
| spellingShingle | Xu Zhou Wen-Ming Liu Han-Yong Sun Yuan Peng Ren-Jie Huang Cai-Yang Chen Hong-Dan Zhang Shen-Ao Zhou Hong-Ping Wu Dan Tang Wei-Jian Huang Han Wu Qi-Gen Li Bo Zhai Qiang Xia Wei-Feng Yu He-Xin Yan Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells Hepatology Communications |
| title | Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells |
| title_full | Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells |
| title_fullStr | Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells |
| title_full_unstemmed | Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells |
| title_short | Hepatocyte-derived liver progenitor-like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells |
| title_sort | hepatocyte derived liver progenitor like cells attenuate liver cirrhosis via induction of apoptosis in hepatic stellate cells |
| url | http://journals.lww.com/10.1097/HC9.0000000000000614 |
| work_keys_str_mv | AT xuzhou hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT wenmingliu hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT hanyongsun hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT yuanpeng hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT renjiehuang hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT caiyangchen hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT hongdanzhang hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT shenaozhou hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT hongpingwu hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT dantang hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT weijianhuang hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT hanwu hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT qigenli hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT bozhai hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT qiangxia hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT weifengyu hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells AT hexinyan hepatocytederivedliverprogenitorlikecellsattenuatelivercirrhosisviainductionofapoptosisinhepaticstellatecells |