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Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells

Paper ID Volume ID Publish Year Pages File Format Full-Text
7373 551 2011 12 PDF Available
Title
Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells
Abstract

Induced pluripotent stem cells (iPSCs) with four reprogramming factors (Oct-4/Sox2/Klf-4/c-Myc) have been shown to differentiate into hepatic lineages. However, it was unclear whether obviation of the c-Myc oncogene in iPSCs affected hepatic differentiation or inhibited in vivo tumor formation. In this study, we demonstrated that iPSCs without c-Myc had the capacity to differentiate into hepatocyte-like cells (iPSC-Heps) with biological functions. As detected using planar-radionuclide imaging and Hoechst labeling assays, these iPSCs and iPSC-Heps tended to mobilize to the injured liver area in thioacetamide (TAA)-treated mice. Intravenous transplantation of both iPSCs and iPSC-Heps but not mouse embryonic fibroblasts (MEFs) reduced the hepatic necrotic area, improved liver functions, and rescued TAA-treated mice from lethal acute hepatic failure (AHF). In addition, microarray-based bioinformatics and quantitative RT-PCR showed high expression of antioxidant genes in iPSCs and iPSC-Heps compared to MEFs. In vivo and in vitro studies of NAC pretreatment confirmed that iPSCs and iPSC-Heps potentially suppressed ROS production and activated antioxidant enzymes in TAA-injured livers. Six months after transplantation in TAA-treated mice, tumor formation was not seen in non-c-Myc iPSC grafts. Therefore, reprogramming adult somatic cells without c-Myc may prevent oxidative stress-induced damage and provide a safer alternative for hepatic regeneration in AHF.

Keywords
Acute hepatic failure; Induced pluripotent stem cell; Reactive oxygen species; HepatocytesAHF, acute hepatic failure; TAA, thioacetamide; MEFs, mouse embryonic fibroblasts; iPSC, induced pluripotent stem cell; iPSC-Hep, induced pluripotent stem cell-deriv
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Reprogramming induced pluripotent stem cells in the absence of c-Myc for differentiation into hepatocyte-like cells
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Publisher
Database: Elsevier - ScienceDirect
Journal: Biomaterials - Volume 32, Issue 26, September 2011, Pages 5994–6005
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us