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Review
. 2020 Dec 8:8:594794.
doi: 10.3389/fcell.2020.594794. eCollection 2020.

Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis

Giulia Chiabotto  1   2 , Chiara Pasquino  1   2 , Giovanni Camussi  1   2 , Stefania Bruno  1   2
Affiliations
Review

Molecular Pathways Modulated by Mesenchymal Stromal Cells and Their Extracellular Vesicles in Experimental Models of Liver Fibrosis

Giulia Chiabotto et al. Front Cell Dev Biol. .

Abstract

End-stage liver fibrosis is common to all chronic liver diseases. Since liver transplantation has several limitations, including lack of donors, immunological rejection, and high medical costs, therapeutic alternatives are needed. The administration of mesenchymal stromal cells (MSCs) has been proven effective in tissue regeneration after damage. However, the risk of uncontrolled side effects, such as cellular rejection and tumorigenesis, should be taken into consideration. A safer alternative to MSC transplantation is represented by the MSC secretome, which retains the same beneficial effect of the cell of origin, without showing any considerable side effect. The paracrine effect of MSCs is mainly carried out by secreted particles in the nanometer range, known as extracellular vesicles (EVs) that play a fundamental role in intercellular communication. In this review, we discuss the current literature on MSCs and MSC-EVs, focusing on their potential therapeutic action in liver fibrosis and on their molecular content (proteins and RNA), which contributes in reverting fibrosis and prompting tissue regeneration.

Keywords: collagen; exosomes; fibrosis; hepatic stellate cell; inflammation; mesenchymal stem cell; microvesicles; α-SMA.

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Conflict of interest statement

GCa is a component of Scientific Advisory Board of Unicyte AG. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Effects of EVs derived from MSCs on inflammatory cells, Kupffer cells, hepatic stellate cells (HSCs), and hepatocytes during liver fibrosis. EVs from MSCs derived from different sources can modulate various molecular pathways in target cells by reducing inflammation, Kupffer cell activation, HSC activation and fibrogenesis, and hepatocyte apoptosis and EMT.
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