Engineering the Vasculature of Stem-Cell-Derived Liver Organoids
Abstract
:1. Introduction
2. Liver Vascularization in Embryonic Development
2.1. Origin of Hepatic Endothelial Cells
2.2. Morphogenesis of Veins, Arteries, and Sinusoids
3. Vascularization and Maturation of Liver Organoids
3.1. Self-Organization in Well Arrays
3.2. Three-Dimensional Bioprinting
3.3. Decellularization
3.4. In Vivo Transplantation
4. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Method | Material | Vascularization Strategy | References |
---|---|---|---|
Self-organization in well arrays | iPSC-HE cells, HUVECs, and BMSCs | Coculture of HUVEC, MSCs, and hPSC-derived hepatic progenitors. MSC-driven condensation on Matrigel | [8] |
Feeder-free human iPSCs | Coculture of iEC, iMSCs, and hiPSC-derived hepatic progenitors iMSC-driven condensation on Matrigel | [23] | |
HAMECs and hiPSCs | EB differentiation of hepatic cells in the presence of HAMEC | [24] | |
MSCs, MSC-derived hepatocytes, and HSC- and LSEC-like cells | Coculture of MSCs, MSC-derived hepatocytes, and HSC- and LSEC-like cells MSC-driven condensation on Matrigel | [25] | |
LPCs and LSECs | Coculture of LPCs and LSECs | [26] | |
Lentivirus vector, hiPSCs, and primary human hepatocytes | Engineering of GRN by lentiviral transduction | [28] | |
Three-dimensional bioprinting | HepG2/C3A cells, EA.hy 926 cells, fabricated alginate solution for cell-laden bioinks and sacrificial materials, lyophilized Atelocollagen, and gelatin powder to form scaffold | Embedding of ECs on a lobule structure with microchannel built by sacrificial material to form an endothelium-lined lumen | [30] |
Liver-bud-like spheroids generated by mature hepatocytes, HUVECs, and MSCs | Coculture of mature hepatocytes, HUVECs, and MSCs | [31] | |
HepaRG cells, sodium alginate solution, and gelatin solution for bioink | In vivo perfusion after transplantation | [32] | |
Decellularization | Liver tissue from mice, rats, ferrets, rabbits, and pigs, 1% Triton-X 100 with 0.1% ammonium hydroxide for decellularization, HUVECs, hFLCs | Seeding ECs on the decellularized liver with a vascular network | [36] |
Porcine liver harvested from 5 to 8 kg piglets, 1% Triton X-100 and 0.1% ammonium hydroxide in distilled water for decellularization, rat anti-mouse CD31 antibody to improve re-endothelialization, and vascular endothelial cells expressing GFP protein (MS1) | Seeding ECs on the decellularized liver with a vascular network | [38] | |
Porcine livers collected from adult pigs (40–50 kg), 1% Triton X-100 and 0.1% ammonium hydroxide in distilled water for decellularization, HG mixture to improve re-endothelialization, human EA.hy926 endothelial cells, hepatic carcinoma cells (HepG2 cells) | Seeding ECs on the decellularized liver with a vascular network | [39] | |
In vivo transplantation | LBs generated from iPSC-HE cells, HUVECs and BMSCs, immunodeficient mice as hosts | Blood perfusion in host body after transplantation | [40] |
LBs generated from LPCs and LSECs, using Fah-/-/Rag2-/-/Il2rg-/- mice as hosts | Blood perfusion in host body after transplantation | [26] | |
LOU prepared from human liver or 2-week-old ActinGFP mice, NOD/SCID γ host mice as hosts | Blood perfusion in host body after transplantation | [41] |
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Zhang, X.; Tang, L.; Yi, Q. Engineering the Vasculature of Stem-Cell-Derived Liver Organoids. Biomolecules 2021, 11, 966. https://doi.org/10.3390/biom11070966
Zhang X, Tang L, Yi Q. Engineering the Vasculature of Stem-Cell-Derived Liver Organoids. Biomolecules. 2021; 11(7):966. https://doi.org/10.3390/biom11070966
Chicago/Turabian StyleZhang, Xv, Liling Tang, and Qian Yi. 2021. "Engineering the Vasculature of Stem-Cell-Derived Liver Organoids" Biomolecules 11, no. 7: 966. https://doi.org/10.3390/biom11070966