Abstract
The current organoid culture systems allow pluripotent and adult stem cells to self-organize to form three-dimensional (3D) structures that provide a faithful recapitulation of the architecture and function of in vivo organs. In particular, human pluripotent stem cell-derived liver organoids (PSC-LOs) can be used in regenerative medicine and preclinical applications, such as disease modeling and drug discovery. New bioengineering tools, such as microfluidics, biomaterial scaffolds, and 3D bioprinting, are combined with organoid technologies to increase the efficiency of hepatic differentiation and enhance the functional maturity of human PSC-LOs by precise control of cellular microenvironment. Long-term stabilization of hepatocellular functions of in vitro liver organoids requires the combination of hepatic endodermal, endothelial, and mesenchymal cells. To improve the biological function and scalability of human PSC-LOs, bioengineering methods have been used to identify diverse and zonal hepatocyte populations in liver organoids for capturing heterogeneous pathologies. Therefore, constructing engineered liver organoids generated from human PSCs will be an extremely versatile tool in in vitro disease models and regenerative medicine in future. In this review, we aim to discuss the recent advances in bioengineering technologies in liver organoid culture systems that provide a timely and necessary study to model disease pathology and support drug discovery in vitro and to generate cell therapy products for transplantation.
Highlights
An organoid is a self-assembled three-dimensional (3D) structure formed by stem/progenitor cells in vitro, which can reproduce many structures and functions of an organ (Lou and Leung, 2018)
Organoids can be generated from pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells, and tissue-specific adult stem cells
We recently developed a Cas9 mRNA-based CRISPR genome editing method to efficiently edit human PSCs (Leung et al, 2020)
Summary
An organoid is a self-assembled three-dimensional (3D) structure formed by stem/progenitor cells in vitro, which can reproduce many structures and functions of an organ (Lou and Leung, 2018). Organoids can be generated from pluripotent stem cells (PSCs), including embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs), and tissue-specific adult stem cells. Various types of organoids have been generated to mimic tissues of heart, intestine, liver, lung, brain, etc. Organoid technology represents a significant enhancement of the 3D culture system. The advantage of organoid cultures is that they are combined with bioengineering technology to mimic target organ structure and environment (Yin et al, 2016), and they contain cell types with in vivo. Despite the wide applications of organoids, tissue microenvironment, such as cell-cell and cell-matrix interactions, need to support complicated regulatory network, which is important to maintain the homeostasis of an organ. Biological engineering methods have enabled us to guide cell communication and cell behavior to analyze how organs work and to reconstruct the system, which are essential processes in organoid establishment
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