Investigation of Hepatoprotective Activity of Induced Pluripotent Stem Cells in the Mouse Model of Liver Injury

Chih-Hung Chiang,Shih-Hwa Chiou,Ping-Hsing Tsai,Shuen-Iu Hung,Hui-Chun Huang,Hsu-Shan Huang,Yi-Jen Chen,Shaw-Yeu Jeng,Jung-Hung Hsieh,Ching-Chih Chang,Shou-Dong Lee,Fa-Yauh Lee

doi:10.1155/2011/219060

Abstract

To date liver transplantation is the only effective treatment for end-stage liver diseases. Considering the potential of pluripotency and differentiation into tridermal lineages, induced pluripotent stem cells (iPSCs) may serve as an alternative of cell-based therapy. Herein, we investigated the effect of iPSC transplantation on thioacetamide- (TAA-) induced acute/fulminant hepatic failure (AHF) in mice. Firstly, we demonstrated that iPSCs had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) that expressed various hepatic markers, including albumin, α-fetoprotein, and hepatocyte nuclear factor-3β, and exhibited biological functions. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal AHF. 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area. Taken together, iPSCs can effectively rescue experimental AHF and represent a potentially favorable cell source of cell-based therapy.

Highlights

Intravenous transplantation of induced pluripotent stem cells (iPSCs) effectively reduced the hepatic necrotic area, improved liver functions and motor activity, and rescued TAA-treated mice from lethal acute/fulminant hepatic failure (AHF). 1, 1 -dioctadecyl-3,3,3, 3 -tetramethylindocarbocyanine perchlorate cell labeling revealed that iPSCs potentially mobilized to the damaged liver area
Acute or fulminant hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with a high mortality rate
The iPSCs were cultured as previously described [17, 18]. iPSCs were seeded at 2 × 104 cells/cm2 maintained in Dulbecco’s modified Eagle’s medium (DMEM; Invitrogen) containing 10% fetal bovine serum, 100 U/mL penicillin, and 100 μg/mL streptomycin in gelatin-coated plates, prior to induction by a 2-step procedure. iPSCs were differentiated by using step-1 differentiating medium, consisting of DMED supplemented with 20 ng/mL HGF (Peprotech), 10 ng/mL bFGF (Peprotech), and 0.61 g/L nicotinamide

Summary

Introduction

Acute or fulminant hepatic failure (AHF) is a severe liver injury accompanied by hepatic encephalopathy which causes multiorgan failure with a high mortality rate. The use of chemical reagents, such as thioacetamide (TAA) [1,2,3,4], acetaminophen [5], or galactosamine [6, 7], may reproduce a number of important clinical characteristics of AHF, such as hypoglycemia, encephalopathy, and increased blood levels of hepatic enzymes. Liver transplantation has been shown to be an effective treatment for this liver failure. The drawback of the procedure is the shortage of donor organs combined with needing the immunosuppressant treatment [8]. Transplantation of hepatocytes or hepatocyte-like cells may provide great promise because cellular therapy is the relative simple and less invasive procedure. The use of embryonic stem cells (ESCs) has attracted attention for cellular therapy because of their capability to proliferation

Methods

Results

Conclusion