A review on the potential of embryonic stem cells in differentiation to hepatocytes
A review on the potential of embryonic stem cells in differentiation to hepatocytes
Tuba Zendehboudi,1Fatemeh Mohajer,2Fatemeh Madadi,3Zohreh Farrar,4Niloofar Dehghan,5Neda Baghban,6,*
1. The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran 2. Student Research and Technology Committee, Bushehr University of Medical Sciences, Bushehr, Iran 3. The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran 4. The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran 5. The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran 6. The Persian Gulf Marine Biotechnology Research Center, The Persian Gulf Biomedical Sciences Research Institute, Bushehr University of Medical Sciences, Bushehr, Iran
Introduction: Embryonic stem cells (ESCs) were first identified in the mouse system and can differentiate into different cell types in vitro. This feature of stem cells has made them a good candidate for novel therapeutics in regenerating damaged tissues and organs. As with other tissues, there is a scarcity of donor livers and hepatocytes, which is compounded by the low recovery and proliferative capacity of adult primary hepatocytes. Besides their potential use for the treatment of liver disease, human embryonic stem cells (HESCs)-derived hepatocytes could be used to study the developmental biology of hepatogenesis.
Methods: The current research is a review on the available literature about differentiation of ESCs in to hepatocytes.
Results: ESCs are derived from the inner cell mass of blastocysts and have the capability of self-renewal and multilineage differentiation. ESC will differentiate and form an EB after removing feeder cells and culturing in suspension culture medium without leukemia inhibitory factor (LIF) or FGF2; The EBs will spontaneously differentiate into different cell types of the three germ layers including liver cells in adherent culture conditions. In order to avoid spontaneous differentiation of ESC forming a mixture of many kinds of cells, researchers have successfully induced ESCs to differentiate into liver cells through the reconstruction of an appropriate in vivo microenvironment. The usual methods utilized to direct differentiation into liver cells fall into three classes: (A) soluble factor-induced approaches, (B) induction via interaction with diverse types of cells, and (C) induction by chromatin modification.
Through gene manipulation hepatic cells were labeled and for the first time, a homogenous population of differentiated cell types was demonstrated. In addition, the hepatic- like cells were suggested to develop in a niche next to cardiac mesodermal cells and that aFGF may play a role in this differentiation.
The differentiation towards hepatic-like cells were also demonstrated by using other factors, added insulin and dexamethasone to EBs cultured on collagen type I and showed that the cells express various endodermal genes.
Conclusion: HESCs have the ability of differentiation into cells with many features of primary human hepatocytes. Hepatocyte-like cells can be enriched and recovered based on asialoglycoprotein-receptor expression and potentially could be applied in drug discovery research and developed as therapeutics.