Tonsil-derived Mesenchymal Stem Cells Ameliorate CCl4–induced Liver Fibrosis in Mice via Autophagy Activation

Abstract

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 liver mesenchymal stem/progenitor cells inhibit hepatic stellate cell activation: in vitro and in vivo evaluation

“…These data were in accordance with a recent study claiming that MSCs are cleared in CCl 4 -damaged livers by 7 days post-transplantation [39] and support the cell-free mechanism of transplanted ADHLSCs in that liver fibrosis model.…”

Differentiated tonsil-derived mesenchymal stem cells embedded in Matrigel restore parathyroid cell functions in rats with parathyroidectomy

“…Although we recently reported that TMSC alone greatly improved liver function in model rats with liver damage induced by concanavalin A [31] or CCl 4 [32], our current data clearly show an important role for use of scaffolds such as Matrigel in recovering parathyroid function in PTX rats. Indeed, without Matrigel, TMSC did not improve parathyroid cell function, suggesting that scaffold and/or its communication with TMSC is likely to determine the success of stem cell therapy, at least in our disease model.…”

Tonsil-Derived Mesenchymal Stem Cells Differentiate into a Schwann Cell Phenotype and Promote Peripheral Nerve Regeneration

“…According to the reports by our group and others, T-MSCs exhibit typical expression patterns of MSC surface markers (negative for CD14, CD34, and CD45; positive for CD73, CD90, and CD105) and have multilineage differentiation potential [14,15,16,17,40]. Previous studies also emphasized the relatively short doubling time of T-MSCs (about 38 h) compared with other types of MSCs (14–17).…”