Preclinical efficacy assessment of umbilical cord mesenchymal stem cell therapy for acute liver failure

Document Type : Original Article

Authors

1 Department of Immunology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China

2 Hangzhou Zhiyuan Research Institute, Zhouhang 310020, Zhejiang, China

3 Zhengzhou Mycelial Protein Biotechnology Co., Ltd, Zhengzhou, 450001, Henan, China

10.22038/ijbms.2025.88181.19046

Abstract

Objective(s): Acute liver failure (ALF) is a life-threatening condition marked by rapid hepatocellular damage. This study investigates the therapeutic efficacy of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) in a rat model of ALF.
Materials and Methods: ALF was induced using D-galactosamine and lipopolysaccharide in rats. hUCMSCs were administered intravenously at different time points and dosages. Liver function, inflammatory cytokine levels, histopathology, neutrophil infiltration, and survival rates were evaluated. Additionally, biodistribution was tracked using 89Zr-labeled hUCMSCs, and fresh versus cryopreserved cells were compared.
Results: Administration of hUCMSCs, especially at the prog-2h time point, significantly improved survival and liver histology. Treatment reduced ALT and AST levels and modulated pro- and anti-inflammatory cytokines. Neutrophil infiltration was alleviated by both fresh and cryo-preserved hUCMSCs. Biodistribution data revealed hepatic enrichment of hUCMSCs peaking at 24 hr post-injection.
Conclusion: hUCMSCs exhibit strong immunomodulatory and hepatoprotective properties in ALF, offering promise for clinical translation. Timing and dosage significantly influence therapeutic efficacy, and cryopreserved cells maintain functionality comparable to that of fresh cells.

Keywords

Main Subjects

References

1. Bernal W, Wendon J. Acute liver failure. N Engl J Med 2013; 369: 2525-2534.
2. Stravitz RT, Lee WMJTL. Acute liver failure. Lancet 2019; 394: 869-881.
3. Lee WM. Acute liver failure. Yamada’s Textbook of Gastroenterology 2022. p. 1889-1905.
4. Liu C, Wang Y-M, Fan K. Epidemiological and clinical features of hepatitis B virus related liver failure in China. World J Gastroenterol 2011; 17: 3054-3059.
5. Jindal A, Sarin SK. Epidemiology of liver failure in Asia‐Pacific region. Liver Int 2022; 42: 2093-2109.
6. Weiler N, Schlotmann A, Schnitzbauer AA, Zeuzem S, Welker M-W. The epidemiology of acute liver failure: Results of a population-based study including 25 million state-insured individuals. Deutsch Ärztebl Int 2020; 117:43-50.
7. Xiao J, Wang F, Wong N-K, He J, Zhang R, Sun R, et al. Global liver disease burdens and research trends: analysis from a Chinese perspective. J Hepatol 2019; 71: 212-221.
8. Liu Y, Ren H, Wang J, Yang F, Li J, Zhou Y, et al. Prostaglandin E2 secreted by mesenchymal stem cells protects against acute liver failure via enhancing hepatocyte proliferation. FASEB J 2019; 33: 2514-2525.
9. de Miguel MP, Prieto I, Moratilla A, Arias J, Aller M. Mesenchymal stem cells for liver regeneration in liver failure: From experimental models to clinical trials. Stem Cells Int 2019; 2019: 3945672-3945684.
10. Zhou T, Yuan Z, Weng J, Pei D, Du X, He C, et al. Challenges and advances in clinical applications of mesenchymal stromal cells. J Hematol Oncol 2021; 14: 1-24.
11. Katarey D, Verma S. Drug-induced liver injury. Clin Med 2016; 16:s104-s109.
12. Soares J-B, Pimentel-Nunes P, Roncon-Albuquerque R, Leite-Moreira A. The role of lipopolysaccharide/toll-like receptor 4 signaling in chronic liver diseases. Hepatol Int 2010; 4: 659-672.
13. Shirozu K, Tokuda K, Marutani E, Lefer D, Wang R, Ichinose F. Cystathionine γ-lyase deficiency protects mice from galactosamine/lipopolysaccharide-induced acute liver failure. Antioxid Redox Signal 2014; 20: 204-216.
14. Zhang S, Yang N, Ni S, Li W, Xu L, Dong P, et al. Pretreatment of lipopolysaccharide (LPS) ameliorates D-GalN/LPS induced acute liver failure through TLR4 signaling pathway. Int J Clin Expl Pathol 2014; 7: 6626-6634.
15. Li M, Zhang J, Fang J, Xin Y, Zhu H, Ding X. Pre-administration of human umbilical cord mesenchymal stem cells has better therapeutic efficacy in rats with D-galactosamine-induced acute liver failure. Int Immunopharmacol 2024; 130:111672.
16. Wang Y-H, Chen E-Q. Mesenchymal stem cell therapy in acute liver failure. Gut Liver 2023; 17: 674-683.
17. Wang S, Wang Y, Xu B, Qin T, Lv Y, Yan H, et al. Biodistribution of 89Zr-oxine-labeled human bone marrow-derived mesenchymal stem cells by micro-PET/computed tomography imaging in Sprague–Dawley rats. Nucl Med Commun 2022; 43: 834-846.
18. Joel MDM, Yuan J, Wang J, Yan Y, Qian H, Zhang X, et al. MSC: Immunoregulatory effects, roles on neutrophils and evolving clinical potentials. Am J Transl Res 2019; 11: 3890-3904.
19. Dave C, Mei SH, McRae A, Hum C, Sullivan KJ, Champagne J, et al. Comparison of freshly cultured versus cryopreserved mesenchymal stem cells in animal models of inflammation: A pre-clinical systematic review. Elife 2022; 11: e75053-705095.
20. Zuo XL, Dongcheng W, Yu D, Sa’ad MA, Teng SLY, Ravichandran M, et al. Isolation, biological characterization, and quality inspection of human umbilical cord-derived mesenchymal stem cells for clinical research. Asian J Biochem Gen Mol Biol 2024; 16: 49-69.
21. Shen D, Wang Z, Wang H, Zhu H, Jiang C, Xie F, et al. Evaluation of preclinical efficacy of human umbilical cord mesenchymal stem cells in ankylosing spondylitis. Front Immunol 2023; 14:1586-1601.
22. Yang J-F, Cao H-C, Pan Q-L, Yu J, Li J, Li L-J. Mesenchymal stem cells from the human umbilical cord ameliorate fulminant hepatic failure and increase survival in mice. Hepatobiliary Pancreat Dis Int 2015; 14: 186-193.
23. Wang Y-H, Wu D-B, Chen B, Chen E-Q, Tang H. Progress in mesenchymal stem cell–based therapy for acute liver failure. Stem Cell Res Ther 2018; 9:1-9.
24. Zhang Y, Li Y, Li W, Cai J, Yue M, Jiang L, et al. Therapeutic effect of human umbilical cord mesenchymal stem cells at various passages on acute liver failure in rats. Stem Cells Int 2018; 2018: 7159465-7159476.
25. Shi M, Liu Z, Wang F. Immunomodulatory properties and therapeutic application of mesenchymal stem cells. Clin Exp Immunol 2011; 164: 1-8.
26. Feng L, Wang Y, Fu Y, Yimamu A, Guo Z, Zhou C, et al. A simple and efficient strategy for cell‐based and cell‐free‐based therapies in acute liver failure: hUCMSCs bioartificial liver. Bioeng Transl Med 2023; 8: e10552-10571.
27. Tang Y, Li Q, Meng F, Huang X, Li C, Zhou X, et al. Therapeutic potential of HGF-expressing human umbilical cord mesenchymal stem cells in mice with acute liver failure. Int J Hepatol 2016; 2016: 5452487-5452500.
28. Wang J. Neutrophils in tissue injury and repair. Cell Tissue Res 2018; 371: 531-539.
29. Chen L, Xiang B, Wang X, Xiang C. Exosomes derived from human menstrual blood-derived stem cells alleviate fulminant hepatic failure. Stem Cell Res Ther 2017; 8: 1-15.
30. Zhu X, He B, Zhou X, Ren J. Effects of transplanted bone-marrow-derived mesenchymal stem cells in animal models of acute hepatitis. Cell Tissue Res 2013; 351: 477-486.
31. Luan Y, Kong X, Feng Y. Mesenchymal stem cells therapy for acute liver failure: recent advances and future perspectives. Liver Res 2021; 5: 53-61.
32. Shi M, Zhang Z, Xu R, Lin H, Fu J, Zou Z, et al. Human mesenchymal stem cell transfusion is safe and improves liver function in acute-on-chronic liver failure patients. Stem Cells Transl Med 2012; 1: 725-731.
33. Zhang S, Yang Y, Fan L, Zhang F, Li L. The clinical application of mesenchymal stem cells in liver disease: The current situation and potential future. Ann Transl Med 2020; 8: 565-575.
34. Peng L, Xie Dy, Lin BL, Liu J, Zhu Hp, Xie C, et al. Autologous bone marrow mesenchymal stem cell transplantation in liver failure patients caused by hepatitis B: Short‐term and long‐term outcomes. Hepatology 2011; 54: 820-828.
Iranian Journal of Basic Medical Sciences
Volume 28, Issue 12
December 2025
Pages 1631-1639

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