Exploring the Efficacy of BMSC Transplantation <i>via</i> Various Pathways for Treating Cholestatic Liver Fibrosis in Mice.

Jun Jie REN; Zi Xu LI; Xin Rui SHI; Ting Ting LYU; Xiao Nan LI; Min GE; Qi Zhi SHUAI; Ting Juan HUANG

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Exploring the Efficacy of BMSC Transplantation via Various Pathways for Treating Cholestatic Liver Fibrosis in Mice.

Author: Jun Jie REN ¹ ; Zi Xu LI ² ; Xin Rui SHI ² ; Ting Ting LYU ³ ; Xiao Nan LI ⁴ ; Min GE ⁵ ; Qi Zhi SHUAI ⁶ ; Ting Juan HUANG ⁷
Author Information

1. Department of Gastroenterology and Hepatology, The First Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
2. Department of Academy of Medical Sciences, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
3. Liver Research Center, Beijing Friendship Hospital, Capital Medical University; Beijing Key Laboratory of Translational Medicine on Liver Cirrhosis; National Clinical Research Center for Digestive Disease, Beijing 100050, China.
4. Department of Cancer Radiotherapy, Fifth Hospital of Shanxi Medical University, Taiyuan 030001, Shanxi, China.
5. School of Clinical Medicine, Medical College, Hebei University of Engineering, Handan 056038, Hebei, China.
6. Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
7. Department of Hepatopancreatobiliary Surgery, First Hospital of Shanxi Medical University Key Laboratory of Birth Defect and Cell Regeneration, Shanxi Medical University, Taiyuan 030001, Shanxi, China.
Publication Type:Journal Article
Keywords: Administration route; Bone marrow mesenchymal stem cells; Cholestatic hepatic fibrosis; Portal vein; Tail vein
MeSH: Animals; Mice; Mesenchymal Stem Cell Transplantation; Liver Cirrhosis/etiology*; Male; Cholestasis/therapy*; Mice, Inbred C57BL; Hepatic Stellate Cells; Mesenchymal Stem Cells
From: Biomedical and Environmental Sciences 2025;38(4):447-458
CountryChina
Language:English
Abstract: OBJECTIVE:To compare the therapeutic efficacy of portal and tail vein transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) against cholestatic liver fibrosis in mice.
METHODS:BMSCs were isolated and co-cultured with starvation-activated hepatic stellate cells (HSCs). HSC activation markers were identified using immunofluorescence and qRT-PCR. BMSCs were injected into the liver tissues of bile duct ligation (BDL) mice via the tail and portal veins. Histomorphology, liver function, inflammatory cytokines, and the expression of key proteins were all determined in the liver tissues.
RESULTS:BMSCs inhibited HSC activation by reducing α-SMA and collagen I expression. Compared to tail vein injection, DIL-labeled BMSCs injected through the portal vein maintained a high homing rate in the liver. Moreover, BMSCs transplanted through the portal vein resulted in greater improvement in liver color, hardness, and gallbladder size than did those transplanted through the tail vein. Furthermore, BMSCs injected by portal vein, but not tail vein, markedly ameliorated liver function, reduced the secretion of inflammatory cytokines, including TNF-α, IL-6, and IL-1β, and decreased α-SMA + hepatic stellate cell (HSC) activation and collagen fiber formation.
CONCLUSION:The therapeutic effect of BMSCs on cholestatic liver fibrosis in mice via portal vein transplantation was superior to that of tail vein transplantation. This comparative study provides reference information for further BMSC studies focused on clinical cholestatic liver diseases.