Abstract
The vasculature of stem-cell-derived liver organoids can be engineered using methods that recapitulate embryonic liver development. Hepatic organoids with a vascular network offer great application prospects for drug screening, disease modeling, and therapeutics. However, the application of stem cell-derived organoids is hindered by insufficient vascularization and maturation. Here, we review different theories about the origin of hepatic cells and the morphogenesis of hepatic vessels to provide potential approaches for organoid generation. We also review the main protocols for generating vascularized liver organoids from stem cells and consider their potential and limitations in the generation of vascularized liver organoids.
Highlights
Liver tissues can regenerate after injury but not after chronic fibrosis or cirrhosis.When these diseases progress to the end stage, the only option for treatment is organ transplantation [1]
Liver organoids have been established from tissue-resident stem/progenitor cells [6], embryonic stem cells [7], and induced pluripotent stem cells [8]
To better direct the vascularization and maturation of liver organoids in vitro, Velazquez et al applied comprehensive analysis and gene regulatory networks (GRNs) engineering to generate pluripotent stem cells (PSCs)-derived multilineage human liver organoids. They engineered the process by which hiPSCs self-organized into a fetal liver organoid (FeLO) by transient lentiviral expression of GATA6
Summary
Liver tissues can regenerate after injury but not after chronic fibrosis or cirrhosis When these diseases progress to the end stage, the only option for treatment is organ transplantation [1]. “Organoid therapy” enables the generation of liver organoids using autologous stem cells and exhibits great potential in the treatment of clinically refractory diseases, such as end-stage liver diseases [4]. LBs generated on well arrays were limited in size and unable to form an intact vascular network. Other protocols such as 3D bioprinting, decellularization, and in vivo transplantation have been developed to generate liver organoids with a larger scale and further vascularization. We review the major protocols for generating vascularized liver organoids from stem cells. We consider the potential and limitations of different protocols in the generation of vascularized liver organoids
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