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

Giulia Chiabotto,Stefania Bruno,Giovanni Camussi,Chiara Pasquino

doi:10.3389/fcell.2020.594794

Giulia Chiabotto, Stefania Bruno + Show 2 more

Open Access

https://doi.org/10.3389/fcell.2020.594794

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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.

Highlights

Chronic liver disease (CLD) may be caused by different types of injury, and it is one of the major global health problems that causes about 2 million deaths per year worldwide (Asrani et al, 2019; Roehlen et al, 2020)
We summarize recent findings in the field of mesenchymal stromal cell (MSC) application as anti-fibrotic strategy and on molecular pathways modulated by MSCs and their secretome, in particular by extracellular vesicle (EV)
In a carbon tetrachloride (CCl4)-induced fibrosis murine model, the BMMSC secretome showed immunosuppressive properties, by reducing inflammatory infiltration, and pro-regenerative effects, by enhancing hepatocyte proliferation and promoting hepatic stellate cell (HSC) apoptosis (Huang et al, 2016). These findings suggest that the anti-fibrogenic effect of MSCs can be mediated through the release of paracrine factors, which include soluble factors and EVs

Summary

Introduction

Chronic liver disease (CLD) may be caused by different types of injury (viral infection, alcohol abuse, NASH, ischemic injury, chemical compounds, autoimmune and genetic diseases, etc.), and it is one of the major global health problems that causes about 2 million deaths per year worldwide (Asrani et al, 2019; Roehlen et al, 2020). Recovery from TAA induced fibrosis by decreasing TGF-β1, type I collagen, and α-SMA expression and modulating the TGF-β1/SMAD signaling pathway Presence of human hepatocyte-like cells in the mouse liver parenchyma attenuating inflammation markers (TNFα).

Results

Conclusion