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

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.

Aquaporin-4 deletion in mice reduces encephalopathy and brain edema in experimental acute liver failure

“…was used to induce ALF as described previously by Jayakumar et al (2011). These mice have been previously characterized with regard to blood levels of glucose, lactate, creatinine, hemoglobin (Sarhan et al, 1993; Caballero et al, 2001; Avraham et al, 2010; Lim JH et al, 2011; Chiang et al, 2011) In brief, TAA was injected i.p. daily for 3 days.…”

Two Effective Routes for Removing Lineage Restriction Roadblocks: From Somatic Cells to Hepatocytes

“…Preliminary transplantation experiments not only confirmed engraftment but also showed teratoma formation, which needs to be excluded using more stringent purification strategies [ 99 ]. Intravenous transplantation of iPSCs effectively reduced the hepatic necrotic area, improved liver function and motor activity, and rescued lethal acute liver failure [ 100 ]. Human iPSCs of distinct origins, regardless of their parental epigenetic memory, can efficiently differentiate along the hepatic lineage to regenerate mouse liver [ 101 , 102 ].…”

Stem Cell Therapy for Liver Diseases

“…Induced pluripotent stem cells used to treat liver disease: Induced pluripotent stem cells (iPSCs) are embryonic like Stem Cells derived from somatic cells [76]. Theoretically, iPSCs could be obtained from the same patient and used for tissue replacement or gene therapy.…”