Liver transplantation is the treatment of choice for chronic liver failure, although it is complicated by donor shortage, surgery-related complications and immunological rejection. Cell transplantation is an alternative, minimally invasive treatment option with potentially fewer complications. We used human palatine tonsil as a novel source of mesenchymal stem cells (T-MSCs) and examined their ability to differentiate into hepatocyte-like cells in vivo and in vitro. Carbon tetrachloride (CCl₄) mouse model was used to investigate the ability of T-MSCs to home to the site of liver injury. T-MSCs were only detected in the damaged liver, suggesting that they are disease-responsive. Differentiation of T-MSCs into hepatocyte-like cells was confirmed in vitro as determined by expression of hepatocyte markers. Next, we showed resolution of liver fibrosis by T-MSCs via reduction of TGF-β expression and collagen deposition in the liver. We hypothesized that autophagy activation was a possible mechanism for T-MSC-mediated liver recovery. In this report, we demonstrate for the first time that T-MSCs can differentiate into hepatocyte-like cells and ameliorate liver fibrosis via autophagy activation and down-regulation of TGF-β. These findings suggest that T-MSCs could be used as a novel source for stem cell therapy targeting liver diseases.

Human mesenchymal stem cells (MSCs) are adult multipotent cells that have plasticity and inhabit the stroma of diverse tissues. The potential utility of MSCs has been heavily investigated in the fields of regenerative medicine and cell therapy. However, MSCs represent diverse populations that may depend on the tissue of origin. Thus, the ability to identify specific MSC populations has remained difficult. Using RNA sequencing, we analyzed the whole transcriptomes of bone marrow-derived MSCs (BMs), adipose tissue-derived MSCs (AMs), and tonsil-derived MSCs (TMs). We categorized highly regulated genes from these MSC groups according to functional gene ontology (GO) classification. AMs and TMs showed higher expression of genes encoding proteins that function in protein binding, growth factor, or cytokine activity in extracellular compartments than BMs. Interestingly, TM were highly enriched for genes coding extracellular, protein-binding proteins compared with AMs. Functional Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis also showed differentially enriched signaling pathways between the three MSC groups. Further, we confirmed surface antigens expressed in common and in a tissue-specific manner on BMs, AMs, and TMs by flow cytometry analysis. This study provides comprehensive characteristics of MSCs derived from different tissues to better understand their cellular and molecular biology.