Recent Advances in Mesenchymal Stem/Stromal Cell-Based Therapy for Alcohol-Associated Liver Disease and Non-alcoholic Fatty Liver Disease

Abstract

Alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) represent pathological conditions that include many distinct stages, potentially leading to the final stage of cirrhotic liver. To date, liver transplantation is the sole successful treatment with concomitant limitations related to donor organ shortage and the need of life-long immunosuppressive therapy. Recently, cell-based therapies for ALD and NAFLD have been proposed with mesenchymal stem/stromal cells (MSCs) as promising effectors. MSC therapeutic applications offer hepatoprotection, regulation of the inflammatory process and angiogenesis particularly in ALD and NAFLD pre-clinical disease models. Recent studies suggested that hepatospecific MSC-based therapies could benefit liver diseases by restoring liver function and decreasing inflammation and fibrosis. Similarly to solid-organ transplantation, limitations in MSC approaches include donor availability exacerbated by high number of cells and cell trapping into lungs. Herein, based on recent advances, we discuss the use of MSCs as a therapeutic approach for ALD and NAFLD and we provide the available information for the establishment of a framework toward a potential clinical application.

Keywords: alcohol-associated liver disease; alcoholic steatohepatitis; cell therapy; fatty liver; mesenchymal stem/stromal cells; non-alcoholic fatty liver disease; non-alcoholic steatohepatitis.

Graphical Abstract

Figure 1.

Treatment of alcohol-associated liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) with use of MSCs. (A) ALD progression and potential MSC-based treatments. (A.1) Administration of both BM-MSCs and Lactobacillus Rhamnosus gg supernatant or (A.2) administration of BM-MSCs and id-BMMs can improve the fibrotic phenotype in ALD or (A.3) Administration of BM-MSCs. (B) NAFLD progression and potential MSC-based treatments. (B.1) Administration of BM-MSCs or UC-MSCs and (B.2) administration of BM-MSCs and id-BMMs can improve the fibrotic phenotype in NAFLD (Created with Biorender.com).