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Regulatory Effect of Mesenchymal Stromal Cells on the Development of Liver Fibrosis: Cellular and Molecular Mechanisms and Prospects for Clinical Application

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Abstract

Liver fibrosis, the progression of which can lead to liver failure, portal hypertension, and hepatocellular carcinoma, is an urgent medical problem. The mechanisms underlying its development include an excessive production of extracellular matrix by activated hepatic-stellate cells, fibrolysis suppression, oxidative damage and apoptosis of hepatocytes, inflammation, and capillarization of the sinusoidal endothelium. The development of the pathological process is caused by the mutual influence of several cell populations through different signaling pathways. At present, the efficiency of the effect on fibrogenesis in liver with the use of pharmacological agents or surgical intervention or the effect of physical factors is low. In this regard, there are high expectations for cell therapy with mesenchymal stromal cells. Their hepatoprotective and regenerative effect is primarily caused by the paracrine secretion of a wide spectrum of regulatory molecules that promote the survival and proliferation of hepatocytes, prevent the activation and stimulate the apoptosis of hepatic-stellate cells, and have immunomodulatory, proangiogenic, and fibrolytic effect. The complex effect of mesenchymal stromal cells on many cell populations involved in the development of liver fibrosis gives reason to consider these cells and their secretory products (particularly, extracellular vesicles) as a promising resource for the clinical use.

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Authors and Affiliations

  1. Sechenov First Moscow State Medical University, Ministry of Health of Russian Federation (Sechenov University), 119991, Moscow, Russia

    O. V. Payushina, D. A. Tsomartova, Y. V. Chereshneva, M. Yu. Ivanova & S. L. Kuznetsov

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  1. O. V. Payushina
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  2. D. A. Tsomartova
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  3. Y. V. Chereshneva
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  4. M. Yu. Ivanova
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Payushina, O.V., Tsomartova, D.A., Chereshneva, Y.V. et al. Regulatory Effect of Mesenchymal Stromal Cells on the Development of Liver Fibrosis: Cellular and Molecular Mechanisms and Prospects for Clinical Application. Biol Bull Rev 11, 54–66 (2021). https://doi.org/10.1134/S2079086421010059

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