Adipose-derived stem cells (ADSCs) are easy to harvest and have the ability for self-renewal and to differentiate into various cell types, including those of the hepatic lineage. Studies on the use of ADSCs for liver transplantation are, however, limited. The objective of this study was to investigate the feasibility of using human ADSCs and to better understand their mechanism of action for the repair of liver damage in a thioacetamide (TAA)-induced model of chronic liver damage in the rat. To induce liver damage, 200 mg/kg TAA was injected intraperitoneally into Wistar rats every 3 days for 60 days. For cell therapy, 1 × 10 6 human ADSCs suspended in 300 ml of phosphate-buffered saline were transplanted into each experimental rat by direct liver injection. Immunohistochemistry showed that the transplanted ADSCs differentiated into albumin-and a-fetoproteinsecreting liver-like cells 1 week after transplantation. In addition, liver function recovered significantly, as determined by biochemical analyses that analyzed total bilirubin, prothrombin time, and albumin levels. The Metavir score, derived from histopathological analysis, also showed a significant decrease in liver fibrosis and inflammatory activity after ADSC transplantation. Finally, we found a reduction in the expression of a-smooth muscle actin, a marker of hepatic stellate cells, which produce collagen fiber, and an increase in the expression of matrix metalloproteinase-9, which degrades collagen fiber, after ADSC transplantation. These findings are consistent with abrogation of liver fibrosis in the ADSC therapy group. Consequently, these results suggest that ADSC transplantation may facilitate recovery from chronic liver damage and thus may have clinical applications.

Objectives: For reasons of provision of highlyspecific surface area and three-dimensional culture, microcarrier culture (MC) has garnered great interest for its potential to expand anchorage-dependent stem cells. This study utilizes MC for in vitro expansion of human bone marrow mesenchymal stem cells (BMMSCs) and analyses its effects on BMMSC proliferation and differentiation. Materials and methods: Effects of semi-continuous MC compared to control plate culture (PC) and serial bead-to-bead transfer MC (MC bead-T) on human BMMSCs were investigated. Cell population growth kinetics, cell phenotypes and differentiation potential of cells were assayed. Results: Maximum cell density and overall fold increase in cell population growth were similar between PCs and MCs with similar starting conditions, but lag period of BMMSC growth differed substantially between the two; moreover, MC cells exhibited reduced granularity and higher CXCR4 expression. Differentiation of BMMSCs into osteogenic and adipogenic lineages was enhanced after 3 days in MC. However, MC bead-T resulted in changes in cell granularity and lower osteogenic and adipogenic differentiation potential. Conclusions: In comparison to PC, MC supported expansion of BMMSCs in an up-scalable threedimensional culture system using a semi-continuous process, increasing potential for stem cell homing ability and osteogenic and adipogenic differentiation.

Currently, there is not an effective therapy for cirrhosis of the liver except for liver transplant. However, finding a compatible liver is difficult due to the low supply and increased demand for healthy livers. Stem cell therapy may be a solution for liver cirrhosis. In our previous report, stem cells from Wharton's jelly and bone marrow were shown to improve liver function in a chemically induced liver fibrosis animal model. However, the immunological rejection of an allograft is always a risk for clinical application. In this study proposal, we suggest using human adipose-derived stem cells (ADSCs) because they are an immune-privileged cell type; they lack human leukocyte antigen-DR expression, and they also suppress the proliferation of activated allogenic lymphocytes and inhibit the production of inflammatory cytokines. In addition, ADSCs contain a sufficient amount of adult stem cells for autologous transplantation. Based on these benefits, ADSCs are promising candidates for clinical application when compared to other stem cell types. The aim of our study will be to investigate the safety and efficacy of autologous ADSCs for the clinical treatment of liver cirrhosis.