Comparing the Therapeutic Mechanism and Immune Response of Human and Mouse Mesenchymal Stem Cells in Immunocompetent Mice With Acute Liver Failure

Chang Hung Wang, Che Yi Chen, Kai Hung Wang, An Pei Kao, Yi Jou Chen, Pei Hsuan Lin, Michael Chen, Tung Yun Wu, Jing Jy Cheng, Kuan Der Lee, Kuo Hsiang Chuang

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

Current mesenchymal stem cell (MSC) research is based on xenotransplantation of human MSCs (hMSCs) in immunodeficient mice and cannot comprehensively predict MSC repair mechanisms and immunomodulatory effects in damaged tissue. This study compared the therapeutic efficacy, mechanisms, and immune response of hMSCs and mouse MSCs (mMSCs) in immunocompetent mice with CCl4-induced acute liver failure. mMSCs maintained F4/80+ hepatic macrophage recruitment into the damaged liver region, increased IL-6-dependent hepatocyte proliferation, and reduced inflammatory TNF-α cytokine secretion. Moreover, mMSCs reduced α-SMA+ myofibroblast activation by lowering TGF-β1 accumulation in damaged liver tissue. In contrast, hMSCs lowered TNF-α and TGF-β1 by reducing the recruitment of F4/80+ hepatic macrophages, which lost the ability to remove debris and induce IL-6 liver regeneration. Finally, hMSCs, but not mMSCs, caused a significant antibody response in immunocompetent mice; therefore, hMSCs are unsuitable for long-term MSC studies. This comparative study provides reference information for further MSC studies of immunocompetent mice.

Original languageEnglish
Pages (from-to)39-53
Number of pages15
JournalStem cells translational medicine
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 30 2023

Keywords

  • F4/80
  • IL-6
  • immunomodulatory
  • liver fibrosis
  • liver regeneration
  • mesenchymal stem cells

ASJC Scopus subject areas

  • General Medicine

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