Adipose-Derived Mesenchymal Stem Cell Therapy for Liver Cirrhosis in Mice

摘要

Mesenchymal stem cells (MSCs) are now an attractive source of cell therapy. We test the hypothesis that autologous adipose-derived mesenchymal stem cells ameliorate liver cirrhosis in mice. In this study, male Swiss mice were treated orally with olive oil or CC14 for 11 weeks (3 times/week). Mouse adipose-derived stem cells (mADSCs) from adipose tissue of mice injuried by CC14 for 3 weeks were cultured prior to transfer by tail vein injection. Hepatocyte-enriched markers were characterized using q-RT-PCR and MSC markers, hepatocyte-enriched proteins, and fibrosis were evaluated by flow cytometry and/or immunohistochemistry. Mice were divided into 4 groups (n = 10 each group): (1) normal, (2) cirrhotic, (3) cirrhotic/PBS, (4) cirrhotic/mADSCs (5 x cells/mice). A separate set of mADSCs was labeled with CFDA to investigate cell homing. The results of in vitro evaluation on mADSCs showed that these cells are highly expression variety of hepatic-related genes such as Hgf, Alb, Ckl8, Ckl9, Cyplal, Afp, MUC1, Ldl receptor and strongly expression of Cyplal and Hgf markers. Dose of 5 x 10~5 cells/animal improved AST/ALT/bilirubin/albumin index after 7 days of injection (p < 0.05); significantly down-regulate gene expression of TGF-beta 1 (14 fold less), procollagen (3 fold less) and nt5e (8 fold less), (p < 0.05). 100% mice improved histology index (HAI modified) and diminished the accumulation of collagen fibers after 21 days compared to 33.3% cirrhotic/PBS. mADSCs "home" to the liver tissue after 21 days.