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Stem Cell-based Therapy Strategy for Hepatic Fibrosis by Targeting Intrahepatic Cells

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Abstract

The whole liver transplantation is the most effective treatment for end-stage fibrosis. However, the lack of available donors, immune rejection and total cost of surgery remain as the key challenges in advancing liver fibrosis therapeutics. Due to the multi-differentiation and low immunogenicity of stem cells, treatment of liver fibrosis with stem cells has been considered as a valuable new therapeutic modality. The pathological progression of liver fibrosis is closely related to the changes in the activities of intrahepatic cells. Damaged hepatocytes, activated Kupffer cells and other inflammatory cells lead to hepatic stellate cells (HSCs) activation, further promoting apoptosis of damaged hepatocytes, while stem cells can work on fibrosis-related intrahepatic cells through relevant transduction pathways. Herein, this article elucidates the phenomena and the mechanisms of the crosstalk between various types of stem cells and intrahepatic cells including HSCs and hepatocytes in the treatment of liver fibrosis. Then, the important influences of chemical compositions, mechanical properties and blood flow on liver fibrosis models with stem cell treatment are emphasized. Clinical trials on stem cell-based therapy for liver fibrosis are also briefly summarized. Finally, continuing challenges and future directions of stem cell-based therapy for hepatic fibrosis are discussed. In short, stem cells play an important advantage and have a great potential in treating liver fibrosis by interacting with intrahepatic cells. Clarifying how stem cells interact with intrahepatic cells to change the progression of liver fibrosis is of great significance for a deeper understanding of liver fibrosis mechanisms and targeted therapy.

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Funding

This work was supported by grants from the National Natural Science Foundation of China (11702044, 11902061), Natural Science Foundation of Chongqing (cstc2020jcyj-msxmX0350), Science and Technology Research Program of Chongqing Municipal Education Commission (KJQN201901114), Visiting Scholar Foundation of Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education (CQKLBST-2020-001), Scientific Research Foundation of Chongqing University of Technology (2019ZD49), and Scientific Research Foundation of Chongqing Technology and Business University (1956016).

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Authors and Affiliations

  1. School of Pharmacy and Bioengineering, Chongqing University of Technology, No. 69 Hongguang Avenue, Banan District, Chongqing, 400054, People’s Republic of China

    Yaxin Deng, Zhongmin Chen, Fuping Wang & Guobao Chen

  2. Chongqing Key Laboratory of Medicinal Chemistry & Molecular Pharmacology, Chongqing University of Technology, Chongqing, 400054, People’s Republic of China

    Yaxin Deng, Zhongmin Chen, Fuping Wang & Guobao Chen

  3. Engineering Research Center for Waste Oil Recovery Technology and Equipment, Ministry of Education, Chongqing Technology and Business University, Chongqing, 400067, People’s Republic of China

    Bin Xia

  4. Mechanobiology and Regenerative Medicine Laboratory, Bioengineering College, Chongqing University, Chongqing, 400044, People’s Republic of China

    Yonggang Lv

  5. State Key Laboratory of New Textile Materials and Advanced Processing Technologies, Wuhan Textile University, Wuhan, 430200, People’s Republic of China

    Yonggang Lv

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  1. Yaxin Deng
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  2. Bin Xia
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  3. Zhongmin Chen
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  4. Fuping Wang
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  5. Yonggang Lv
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  6. Guobao Chen
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G. C. and Y. D. conceptualized the idea. Y. D., B. X., Z. C., F. W., Y. L. and G. C. wrote the manuscript and approved the final version of the manuscript.

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Correspondence to Guobao Chen.

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Deng, Y., Xia, B., Chen, Z. et al. Stem Cell-based Therapy Strategy for Hepatic Fibrosis by Targeting Intrahepatic Cells. Stem Cell Rev and Rep 18, 77–93 (2022). https://doi.org/10.1007/s12015-021-10286-9

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