Editorial
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2015; 21(21): 6427-6433
Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6427
Cell therapy from bench to bedside: Hepatocytes from fibroblasts - the truth and myth of transdifferentiation
Madhusudana Girija Sanal
Madhusudana Girija Sanal, Department of Radiation Oncology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY 10461, United States
Author contributions: Sanal MG conceived the issues which formed the content of the manuscript and wrote the manuscript.
Supported by IIP fellowship (2013-2014), Albert Einstein College of Medicine, New York, through the generosity of the Gruss Lipper Family Foundation.
Conflict-of-interest: The author has no conflict of interests.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Madhusudana Girija Sanal, MBBS, PhD, Department of Radiation Oncology, Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Room 323, Ullmann Building, 1300 Morris Park Avenue, Bronx, NY 10461, United States. sanalmg@gmail.com
Telephone: +1-347-3894440 Fax: +1-718-4303099
Received: December 4, 2014
Peer-review started: December 5, 2014
First decision: March 10, 2015
Revised: March 24, 2015
Accepted: May 7, 2015
Article in press: May 7, 2015
Published online: June 7, 2015
Abstract

Hepatocyte transplantation is an alternative to liver transplantation in certain disorders such as inherited liver diseases and liver failure. It is a relatively less complicated surgical procedure, and has the advantage that it can be repeated several times if unsuccessful. Another advantage is that hepatocytes can be isolated from partly damaged livers which are not suitable for liver transplantation. Despite these advantages hepatocyte transplantation is less popular. Important issues are poor engraftment of the transplanted cells and the scarcity of donor hepatocytes. Generation of “hepatocyte like cells”/iHeps from embryonic stem cells (ES) and induced pluripotent stem cells (iPSCs) by directed differentiation is an emerging solution to the latter issue. Direct conversation or trans-differentiation of fibroblasts to “hepatocyte like cells” is another way which is, being explored. However this method has several inherent and technical disadvantages compared to the directed differentiation from ES or iPSC. There are several methods claiming to be “highly efficient” for generating “highly functional”“hepatocyte like cells”. Currently different groups are working independently and coming up with differentiation protocols and each group claiming an advantage for their protocol. Directed differentiation protocols need to be designed, compared, analyzed and tweaked systematically and logically than empirically. There is a need for a well-coordinated global initiative comparable to the Human Genome Project to achieve this goal in the near future.

Keywords: Trans differentiation, i-Heps, Fibroblasts, Induced pluripotent stem cells, Embryonic stem cells, Hepatocyte like cells, Telomere/telomerase, Hepatocyte transplantation, differentiation, Inherited/genetic liver disease, Cell therapy, Gene therapy

Core tip: Hepatocyte transplantation is an alternative for liver transplantation in chronic liver disease patients for a long term cure. There is a scarcity of donor liver and hepatocytes. Induced pluripotent stem cells (iPSC) derived hepatocytes and hepatocytes generated by transdifferentiation are two possibilities. iPSC derived hepatocytes often fail to engraft upon transplantation. We need to define methods to evaluate and compare efficiency of differentiation, standards and clear quality definition for hepatocyte like cells. More comprehensive analysis of the RNAs and proteome is required. Methods to compare and analyze the expression profiles, standards and references to be compared with need to be defined. There is a need for a well-coordinated global initiative comparable to the scale of the Human Genome Project to achieve this goal in the near future.