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

doi:10.1093/stcltm/szac084

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 journal › Article › peer-review

6 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 language	English
Pages (from-to)	39-53
Number of pages	15
Journal	Stem cells translational medicine
Volume	12
Issue number	1
DOIs	https://doi.org/10.1093/stcltm/szac084
Publication status	Published - 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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10.1093/stcltm/szac084

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Wang, C. H., Chen, C. Y., Wang, K. H., Kao, A. P., Chen, Y. J., Lin, P. H., Chen, M., Wu, T. Y., Cheng, J. J., Lee, K. D., & Chuang, K. H. (2023). Comparing the Therapeutic Mechanism and Immune Response of Human and Mouse Mesenchymal Stem Cells in Immunocompetent Mice With Acute Liver Failure. Stem cells translational medicine, 12(1), 39-53. https://doi.org/10.1093/stcltm/szac084

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

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.",

keywords = "F4/80, IL-6, immunomodulatory, liver fibrosis, liver regeneration, mesenchymal stem cells",

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

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AU - Chen, Yi Jou

AU - Lin, Pei Hsuan

AU - Chen, Michael

AU - Wu, Tung Yun

AU - Cheng, Jing Jy

AU - Lee, Kuan Der

AU - Chuang, Kuo Hsiang

N1 - Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press.

PY - 2023/1/30

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N2 - 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.

AB - 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.

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

Abstract

Keywords

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