Suppression of Carbon Tetrachloride-Induced Liver Fibrosis by Transplantation of a Clonal Mesenchymal Stem Cell Line Derived from Rat Bone Marrow

Abstract

Transplantation of hepatocytes or bone marrow-derived cells has been shown to ameliorate liver fibrosis in animal models, but no direct comparison of relative efficiency has been made. The aim of this study was to compare the efficiency of a bone marrow-derived clonal mesenchymal stem cell line established by us (rBM25/S3) with that of its adipogenic or hepatogenic differentiation derivative for suppression of rat liver fibrosis. After induction of differentiation of rBM25/S3 cells into adipogenic or hepatogenic cells in culture, we intrasplenically transplanted the three types of cells into rats (3 x 10(7) cells/rat) before and 4 weeks after initiation of carbon tetrachloride treatment (1 ml/kg body weight twice a week for 8 weeks) to induce liver fibrosis. Undifferentiated rBM25/S3 cells were the most effective for suppression of liver fibrosis, followed by the adipogenic cells and hepatogenic cells. Expression levels of MMP-2 and MMP-9 were also highest in undifferentiated rBM25/S3 cells. These results indicate that bone marrow-derived clonal mesenchymal stem cell lines are useful for further mechanistic studies on cell-mediated suppression of liver fibrosis and that such cell lines will provide information on an appropriate cell source for transplantation therapy for cirrhosis.

Therapeutic Strategies of Stem Cell Transplantation for Liver Cirrhosis

“…Based on the published results, thoroughly predifferentiated stem cells appear to be less potent than unpredifferentiated cells [27] [28], and hepatocyte transplantation appears to be less effective than stem cell transplantation [32].…”

Treating end-stage liver diseases with mesenchymal stem cells: An oak is not felled at one stroke

“…(c) MSCs may dissolve ibrosis directly. There was evidence suggesting that MSCs were able to produce the matrix metalloproteinase (MMPs), an enzyme capable of degrading the extracellular matrix, which alleviates hepatic cirrhosis directly 21 . However, there is still a long way to go before MSC therapy can achieve signi icant improvement in both function and histology of liver cirrhosis.…”

Therapeutic potential of adipose tissue-derived multi-lineage progenitor cell-sheets on liver fibrosis

“…Mesenchymal stem cells, which possess certain characteristics including self-renewal, proliferation, differentiation and/or secretion of bio-active cytokines, are promising tools in cell therapy [14]. The effectiveness of bone marrow or adipose tissue-derived cells in animal models of liver fibrosis and cirrhosis have been demonstrated by several groups including us [14,[15][16][17][18][19][20]. However, others have reported the lack of any changes in the extent of liver fibrosis or liver function tests following the use of BM-MSCs in the animal models of severe chronic liver injury [21].…”

“…Major part of previous reports demonstrated their routes of administration were intravenous [14,[16][17][18][19][20]. The intravenously administered cells have reported to be accumulated to the lung and then the liver with loss of administrated cell numbers [24], resulted in reduction of efficacy.…”