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  3. Bone marrow mesenchymal stem cells alleviate liver fibrosis after rat liver transplantation through JAK1/STAT5 pathway

Bone marrow mesenchymal stem cells alleviate liver fibrosis after rat liver transplantation through JAK1/STAT5 pathway

  • Stem Cell Res Ther. 2025 May 1;16(1):217. doi: 10.1186/s13287-025-04353-y.
Zhuyuan Si # 1 2,  Shengqiao Zhao # 2,  Zhixin Zhang # 2,  Tianran Chen 2,  Ruofan Wang 2,  Chong Dong 2,  Kai Wang 2,  Chao Sun 2,  Zhuolun Song 2 3,  Zhongyang Shen 4 5,  Wei Gao 6 7
Affiliations

Affiliations

  • 1 Department of Organ Transplantation, Qilu Hospital of Shandong University, Jinan, China.
  • 2 Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China.
  • 3 Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China.
  • 4 Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China. zhyshentjfch@sina.com.
  • 5 Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China. zhyshentjfch@sina.com.
  • 6 Department of Liver Transplantation, Organ Transplantation Center, Tianjin First Central Hospital, Tianjin, China. gaowei_tjfch@163.com.
  • 7 Tianjin Key Laboratory of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China. gaowei_tjfch@163.com.
  • # Contributed equally.
PMID: 40312752 DOI: 10.1186/s13287-025-04353-y
Abstract

Objective: The effectiveness of bone marrow mesenchymal stem cells (BMSCs) in post-transplantation liver fibrosis has not been studied. The aim of this study was to investigate the effect of BMSCs on liver fibrosis and their role in the Janus-activated kinase (JAK) 1/ signal transducer and activator of transcription (STAT) 5 pathway after liver transplantation (LT).

Methods: A rat model of post-LT liver fibrosis induced by cold ischemia injury was successfully established. BMSCs were injected into the rats through the portal vein. Hepatic stellate cell (HSC)-T6 were co-cultured with BMSCs in vitro after hypoxia-reoxygenation. JAK1 Inhibitor Abrocitinib and JAK1 agonist RO8191 were used to study the JAK1/STAT5 signaling pathway.

Results: BMSCs significantly alleviated liver fibrosis caused by cold ischemia-reperfusion injury after rat LT in vivo. After BMSCs transplantation, the levels of JAK1 and p-STAT5 in rat liver were significantly reduced. After using Abrocitinib, the stage of liver fibrosis and the levels of Collagen type I alpha 1 chain (COL1A1) and actin alpha 2 (ACTA2) decreased. After using RO8191, the stage of liver fibrosis and the levels of COL1A1 and ACTA2 increased. BMSCs significantly reduced the activation of HSC-T6 after hypoxia-reoxygenation in vitro. After co-culturing with BMSCs after HSC-T6 hypoxia-reoxygenation, the levels of JAK1 and p-STAT5 were significantly reduced. After the addition of Abrocitinib, the levels of COL1A1 and ACTA2 decreased in HSC-T6; in contrast, after adding RO8191, the levels of COL1A1 and ACTA2 increased in HSC-T6 after hypoxia-reoxygenation. After using anti-IL7 antibody or anti-IL7Rα in vivo and in vitro, the stage of liver fibrosis and the levels of COL1A1 and ACTA2 decreased as well as the phosphorylation level of STAT5.

Conclusions: BMSCs alleviate hepatic cell damage, reduce hepatic cell-derived IL7, downregulate IL7R/JAK1/STAT5 in HSCs, thereby reducing HSCs' activation and ultimately alleviating liver fibrosis after liver transplantation.

Keywords

Bone marrow mesenchymal stem cells; Hepatic stellate cells; JAK1; Liver fibrosis; Liver transplantation; STAT5.

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