A cMet Inhibitor Promotes the Survival and Long‐Term Efficacy of Transplanted Hepatic Stem/Progenitor Cells in Liver Cirrhosis
5 affiliations
- 1Department of Special Medicine Shanxi Medical University Taiyuan City 030001 Sanxi Province China sxmu.edu.cn
- 2College of Bioengineering Chongqing University Chongqing City 400044 China cqu.edu.cn
- 3Hepatobiliary Institute Southwest Hospital Army Medical University Chongqing City 400038 China tmmu.edu.cn
- 4Beijing Key Laboratory Research on Liver Regeneration and Artificial Liver Transplantation Beijing You’an Hospital Capital Medical University Beijing City 100069 China ccmu.edu.cn
- 5Department of Hepatobiliary Surgery Chongqing Hygeia Hospital Chongqing City 401147 China
Abstract
Background: Poor retention of transplanted stem cells in the liver cirrhosis milieu (LCM) which critically blunts long‐term efficacy, remains unexplained. This study investigated the effects of a small peptide chemical compound (icMet) delivered intravenously for cMet receptor inhibition at the diethylnitrosamine (DEN)‐induced middle‐to‐late cirrhotic liver stage (CLS8/9), focusing on apoptosis prevention, endogenous hepatic regeneration and the long‐term efficacy of transplanted hepatic stem/progenitor cells (MLpvNG2 cells).
Methods: C57BL/6 mice with CLS8/9 liver injury were used as recipients. icMet was used before or during MLpvNG2 cell therapy. Tissues from CLS8/9 livers were also used to generate conditioned medium (CM, CLS8/9CM) to observe MLpvNG2 cell activity in response to the injured liver‐related cues. Results: Compared with CLS8/9 mice without icMet, mice subjected to icMet administration showed increased survival rates of transplanted MLpvNG2 cells in the CLS8/9 livers, as well as enhanced downstream hepatic repair and long‐term healing. In CLS8/9CM cultures, the survival of MLpvNG2 cells within icMet was similar to that observed in CLS8/9 livers. In terms of the underlying mechanisms, it is possible that icMet pretreatment promotes proliferation and prevents apoptosis of grafted MLpvNG2 cells, activating host hepatic functional differentiation, particularly sinusoidal reconstruction, which can initiate hepatocyte regeneration. In addition, the relieved fibrotic load could also favor repopulation by donor cells, leading to long‐term treatment efficacy.
Conclusions: A strategy involving a pre‐ or during cell treatment that blocks the cMet receptor achieves apoptosis resistance of transplanted MLpvNG2 cells in the LCM and promotes endogenous hepatic regeneration, leading to long‐term treatment efficacy.
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BibTeX
@article{yan2026cmet,
title = {{A cMet Inhibitor Promotes the Survival and Long‐Term Efficacy of Transplanted Hepatic Stem/Progenitor Cells in Liver Cirrhosis}},
author = {Min Yan and Deyu Hu and Jiejuan Lai and Quanyu Chen and Jiayu Yu and Mei Ding and Lu Li and Hongbo Shi and Hongyu Zhang and Yu Chen and Lianhua Bai},
journal = {Stem Cells International},
year = {2026},
month = oct,
doi = {10.1155/sci/7020341},
url = {https://doi.org/10.1155/sci/7020341},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - A cMet Inhibitor Promotes the Survival and Long‐Term Efficacy of Transplanted Hepatic Stem/Progenitor Cells in Liver Cirrhosis
AU - Min Yan
AU - Deyu Hu
AU - Jiejuan Lai
AU - Quanyu Chen
AU - Jiayu Yu
AU - Mei Ding
AU - Lu Li
AU - Hongbo Shi
AU - Hongyu Zhang
AU - Yu Chen
AU - Lianhua Bai
PY - 2026
DA - 2026/10/30
JO - Stem Cells International
DO - 10.1155/sci/7020341
UR - https://doi.org/10.1155/sci/7020341
AB - Background: Poor retention of transplanted stem cells in the liver cirrhosis milieu (LCM) which critically blunts long‐term efficacy, remains unexplained. This study investigated the effects of a small peptide chemical compound (icMet) delivered intravenously for cMet receptor inhibition at the diethylnitrosamine (DEN)‐induced middle‐to‐late cirrhotic liver stage (CLS8/9), focusing on apoptosis prevention, endogenous hepatic regeneration and the long‐term efficacy of transplanted hepatic stem/progenitor cells (MLpvNG2 cells). Methods: C57BL/6 mice with CLS8/9 liver injury were used as recipients. icMet was used before or during MLpvNG2 cell therapy. Tissues from CLS8/9 livers were also used to generate conditioned medium (CM, CLS8/9CM) to observe MLpvNG2 cell activity in response to the injured liver‐related cues. Results: Compared with CLS8/9 mice without icMet, mice subjected to icMet administration showed increased survival rates of transplanted MLpvNG2 cells in the CLS8/9 livers, as well as enhanced downstream hepatic repair and long‐term healing. In CLS8/9CM cultures, the survival of MLpvNG2 cells within icMet was similar to that observed in CLS8/9 livers. In terms of the underlying mechanisms, it is possible that icMet pretreatment promotes proliferation and prevents apoptosis of grafted MLpvNG2 cells, activating host hepatic functional differentiation, particularly sinusoidal reconstruction, which can initiate hepatocyte regeneration. In addition, the relieved fibrotic load could also favor repopulation by donor cells, leading to long‐term treatment efficacy. Conclusions: A strategy involving a pre‐ or during cell treatment that blocks the cMet receptor achieves apoptosis resistance of transplanted MLpvNG2 cells in the LCM and promotes endogenous hepatic regeneration, leading to long‐term treatment efficacy.
SN - 1687-966X
SN - 1687-9678
ER -