Review Article

Mesenchymal stem cells in fibrotic diseases—the two sides of the same coin

Lei Qin1, Nian Liu1, Chao-le-meng Bao2, Da-zhi Yang1, Gui-xing Ma3, Wei-hong Yi1, Guo-zhi Xiao3, Hui-ling Cao3
1 Department of Orthopedics, Huazhong University of Science and Technology Union Shenzhen Hospital, Shenzhen 518000, China
2 CASTD Regengeek (Shenzhen) Medical Technology Co. Ltd, Shenzhen 518000, China
3 Department of Biochemistry, School of Medicine, Southern University of Science and Technology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Shenzhen 518055, China
Correspondence to: Wei-hong Yi:, Guo-zhi Xiao:, Hui-ling Cao:,
DOI: 10.1038/s41401-022-00952-0
Received: 19 February 2022
Accepted: 29 June 2022
Advance online: 27 July 2022


Fibrosis is caused by extensive deposition of extracellular matrix (ECM) components, which play a crucial role in injury repair. Fibrosis attributes to ~45% of all deaths worldwide. The molecular pathology of different fibrotic diseases varies, and a number of bioactive factors are involved in the pathogenic process. Mesenchymal stem cells (MSCs) are a type of multipotent stem cells that have promising therapeutic effects in the treatment of different diseases. Current updates of fibrotic pathogenesis reveal that residential MSCs may differentiate into myofibroblasts which lead to the fibrosis development. However, preclinical and clinical trials with autologous or allogeneic MSCs infusion demonstrate that MSCs can relieve the fibrotic diseases by modulating inflammation, regenerating damaged tissues, remodeling the ECMs, and modulating the death of stressed cells after implantation. A variety of animal models were developed to study the mechanisms behind different fibrotic tissues and test the preclinical efficacy of MSC therapy in these diseases. Furthermore, MSCs have been used for treating liver cirrhosis and pulmonary fibrosis patients in several clinical trials, leading to satisfactory clinical efficacy without severe adverse events. This review discusses the two opposite roles of residential MSCs and external MSCs in fibrotic diseases, and summarizes the current perspective of therapeutic mechanism of MSCs in fibrosis, through both laboratory study and clinical trials.
Keywords: fibrotic diseases; mesenchymal stem cells; myofibroblasts; liver cirrhosis; pulmonary fibrosis

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