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World J Gastroenterol. Jun 14, 2013; 19(22): 3385-3396
Published online Jun 14, 2013. doi: 10.3748/wjg.v19.i22.3385
Thinking outside the liver: Induced pluripotent stem cells for hepatic applications
Mekala Subba Rao, Mitnala Sasikala, D Nageshwar Reddy
Mekala Subba Rao, Mitnala Sasikala, Institute of Basic Sciences and Translational Research, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad 500082, India
D Nageshwar Reddy, Asian Healthcare Foundation, Asian Institute of Gastroenterology, Hyderabad 500082, India
Author contributions: Subba Rao M and Sasikala M performed the research and wrote the paper; Reddy DN contributed information and helped to design the paper.
Supported by Asian Healthcare Foundation, Hyderabad, India
Correspondence to: Dr. D Nageshwar Reddy, Chairman, Asian Healthcare Foundation, Asian Institute of Gastroenterology, 6-3-661, Somajiguda, Hyderabad 500082, India.
Telephone: +91-40-23378888 Fax: +91-40-23324255
Received: August 15, 2011
Revised: December 6, 2011
Accepted: December 15, 2011
Published online: June 14, 2013

The discovery of induced pluripotent stem cells (iPSCs) unraveled a mystery in stem cell research, after identification of four re-programming factors for generating pluripotent stem cells without the need of embryos. This breakthrough in generating iPSCs from somatic cells has overcome the ethical issues and immune rejection involved in the use of human embryonic stem cells. Hence, iPSCs form a great potential source for developing disease models, drug toxicity screening and cell-based therapies. These cells have the potential to differentiate into desired cell types, including hepatocytes, under in vitro as well as under in vivo conditions given the proper microenvironment. iPSC-derived hepatocytes could be useful as an unlimited source, which can be utilized in disease modeling, drug toxicity testing and producing autologous cell therapies that would avoid immune rejection and enable correction of gene defects prior to cell transplantation. In this review, we discuss the induction methods, role of reprogramming factors, and characterization of iPSCs, along with hepatocyte differentiation from iPSCs and potential applications. Further, we discuss the location and detection of liver stem cells and their role in liver regeneration. Although tumor formation and genetic mutations are a cause of concern, iPSCs still form a promising source for clinical applications.

Keywords: Liver stem cells, Hepatocytes, Disease modeling, Drug toxicity, Clinical applications, Patient-specific induced pluripotent stem cell-derived hepatocytes