Mesenchymal stromal cells (MSCs) and their exosome in acute liver failure (ALF): a comprehensive review

Abstract

Recently, mesenchymal stromal cells (MSCs) and their derivative exosome have become a promising approach in the context of liver diseases therapy, in particular, acute liver failure (ALF). In addition to their differentiation into hepatocytes in vivo, which is partially involved in liver regeneration, MSCs support liver regeneration as a result of their appreciated competencies, such as antiapoptotic, immunomodulatory, antifibrotic, and also antioxidant attributes. Further, MSCs-secreted molecules inspire hepatocyte proliferation in vivo, facilitating damaged tissue recovery in ALF. Given these properties, various MSCs-based approaches have evolved and resulted in encouraging outcomes in ALF animal models and also displayed safety and also modest efficacy in human studies, providing a new avenue for ALF therapy. Irrespective of MSCs-derived exosome, MSCs-based strategies in ALF include administration of native MSCs, genetically modified MSCs, pretreated MSCs, MSCs delivery using biomaterials, and also MSCs in combination with and other therapeutic molecules or modalities. Herein, we will deliver an overview regarding the therapeutic effects of the MSCs and their exosomes in ALF. As well, we will discuss recent progress in preclinical and clinical studies and current challenges in MSCs-based therapies in ALF, with a special focus on in vivo reports.

Keywords: Acute liver failure (ALF); Exosome; Hepatocyte; Immunomodulation; Mesenchymal stromal cell (MSCs).

Fig. 1

Underlying mechanism complicated in mesenchymal stromal cells (MSCs) migration to damaged liver tissue. The connections between CXCR4 and SDF-1ɑ, c-Met and HGF, and finally VLA-4 and VCAM-1 underlie cell to cell interaction between endothelial cells (ECs) and MSCs, which, in turn, facilitate MSCs migration to damaged liver tissue. Then MSCs secrete anti-inflammatory molecules, such as PGE2, IDO, TGF-β, IL-10, and NO to down-regulate inflammation. These molecules prompt the change of inflammatory to proliferating phase largely defined by the secretion of PDGF and VEGF, sustaining hepatocyte formation and proliferation

Fig. 2

Clinical trials based on mesenchymal stromal cells (MSCs) therapy in liver-associated conditions registered in ClinicalTrials.gov (November 2021). The schematic demonstrates clinical depending on the study phase (A), study status (B), MSCs source (C), study location (D), participant number (E), and condition (F)