Abstract
The conversion of somatic cells to hepatocytes has fundamentally re-shaped traditional concepts regarding the limited resources for hepatocyte therapy. With the various induced pluripotent stem cell (iPSC) generation routes, most somatic cells can be effectively directed to functional stem cells, and this strategy will supply enough pluripotent material to generate promising functional hepatocytes. However, the major challenges and potential applications of reprogrammed hepatocytes remain under investigation. In this review, we provide a summary of two effective routes including direct reprogramming and indirect reprogramming from somatic cells to hepatocytes and the general potential applications of the resulting hepatocytes. Through these approaches, we are striving toward the goal of achieving a robust, mature source of clinically relevant lineages.
Highlights
As the largest organ in the human body, the liver performs multiple metabolic functions, including detoxification, glucose metabolism, plasma protein synthesis, and bile production [1]
We provide a summary of two effective routes including direct reprogramming and indirect reprogramming from somatic cells to hepatocytes and the general potential applications of the resulting hepatocytes
When combined with the capacity to engineer genetic changes in established Induced pluripotent stem cells (iPSCs) [123], patient-specific iPSCs and hepatocyte-like cells (HLCs) can be utilized to study genetic variants identified in Genome-wide association studies (GWAS) studies as well as a host of other monogenic alterations to assay their impact on hepatocyte differentiation, phenotype, and function [124], facilitating the in vitro tmodeling of rare diseases
Summary
As the largest organ in the human body, the liver performs multiple metabolic functions, including detoxification, glucose metabolism, plasma protein synthesis, and bile production [1]. Induced pluripotent stem cells (iPSCs) were first generated by Yamanaka and colleagues following the forced expression of four transcription factors (OCT3/4, SOX2, C-MYC, and KLF4) in somatic cells [5]. Upon manipulation of their culture conditions in vitro or their transplantation into mice, iPSCs can be differentiated into numerous endodermal lineages, including hepatocytes [6]. Combining all the optimized conditions such as the suitable cell source; excellent combination of reprogramming factors, non-integrated vectors or excisable vectors; and feeder-free culture systems or 3D culture systems, iPSCs can be safely generated and differentiated to other lineages for research or clinical applications
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