Current Issue

Volume 19, Number 2, Summer 2017, Serial Number: 74 Pages: 204-217

In Vitro Generated Hepatocyte-Like Cells: A Novel Tool in Regenerative Medicine and Drug Discovery


Kobra Zakikhan, Ph.D, 1, Behshad Pournasr, Ph.D, 2, Massoud Vosough, M.D.,Ph.D, 3, *, Marjan Nassiri-Asl, Pharm.D.و Ph.D, 1, 4, *,
Cellular and Molecular Research Center, Department of Molecular Medicine, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Department of Regenerative Biomedicine, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
Cellular and Molecular Research Center, Department of Pharmacology, School of Medicine, Qazvin University of Medical Sciences, Qazvin, Iran
*Corresponding Addresses: P.O.Box: 16635-148 Department of Regenerative Biomedicine Cell Science Research Center Royan Institute for Stem Cell Biology and Technology ACECR TehranIran P.O.Box: 341197-5981 Cellular and Molecular Research Center Department of Pharmacology School of Medicine Qazvin University of Medical Sciences Qazvin Iran Emails:masvos@RoyanInstitute.org,mnassiriasl@qums.ac.ir

Abstract

Hepatocyte-like cells (HLCs) are generated from either various human pluripotent stem cells (hPSCs) including induced pluripotent stem cells (iPSCs) and embryonic stem cells (ESCs), or direct cell conversion, mesenchymal stem cells as well as other stem cells like gestational tissues. They provide potential cell sources for biomedical applications. Liver transplantation is the gold standard treatment for the patients with end stage liver disease, but there are many obstacles limiting this process, like insufficient number of donated healthy livers. Meanwhile, the number of patients receiving a liver organ transplant for a better life is increasing. In this regard, HLCs may provide an adequate cell source to overcome these shortages. New molecular engineering approaches such as CRISPR/ Cas system applying in iPSCs technology provide the basic principles of gene correction for monogenic inherited metabolic liver diseases, as another application of HLCs. It has been shown that HLCs could replace primary human hepatocytes in drug discovery and hepatotoxicity tests. However, generation of fully functional HLCs is still a big challenge; several research groups have been trying to improve current differentiation protocols to achieve better HLCs according to morphology and function of cells. Large-scale generation of functional HLCs in bioreactors could make a new opportunity in producing enough hepatocytes for treating end-stage liver patients as well as other biomedical applications such as drug studies. In this review, regarding the biomedical value of HLCs, we focus on the current and efficient approaches for generating hepatocyte-like cells in vitro and discuss about their applications in regenerative medicine and drug discovery.