Human Pluripotent-stem-cell-derived Organoids for Drug Discovery and Evaluation

Overview

Journal Cell Stem Cell

Publisher Cell Press

Specialty Cell Biology

Date 2023 May 5

PMID 37146581

Authors

J Jeya Vandana

Cassandra Manrique

Lauretta A Lacko

Shuibing Chen

Affiliations

Soon will be listed here.

Abstract

Human pluripotent stem cells (hPSCs) and three-dimensional organoids have ushered in a new era for disease modeling and drug discovery. Over the past decade, significant progress has been in deriving functional organoids from hPSCs, which have been applied to recapitulate disease phenotypes. In addition, these advancements have extended the application of hPSCs and organoids for drug screening and clinical-trial safety evaluations. This review provides an overview of the achievements and challenges in using hPSC-derived organoids to conduct relevant high-throughput, high-contentscreens and drug evaluation. These studies have greatly enhanced our knowledge and toolbox for precision medicine.

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References

Leibel S, Winquist A, Tseu I, Wang J, Luo D, Shojaie S . Reversal of Surfactant Protein B Deficiency in Patient Specific Human Induced Pluripotent Stem Cell Derived Lung Organoids by Gene Therapy. Sci Rep. 2019; 9(1):13450. PMC: 6748939. DOI: 10.1038/s41598-019-49696-8. View

Wu B, Yang Z, Liu Y, Li J, Chen C, Li X . A chemically defined system supports two distinct types of stem cell from a single blastocyst and their self-assembly to generate blastoid. Cell Prolif. 2023; 56(6):e13396. PMC: 10280139. DOI: 10.1111/cpr.13396. View

Wimmer R, Leopoldi A, Aichinger M, Wick N, Hantusch B, Novatchkova M . Human blood vessel organoids as a model of diabetic vasculopathy. Nature. 2019; 565(7740):505-510. PMC: 7116578. DOI: 10.1038/s41586-018-0858-8. View

Strikoudis A, Cieslak A, Loffredo L, Chen Y, Patel N, Saqi A . Modeling of Fibrotic Lung Disease Using 3D Organoids Derived from Human Pluripotent Stem Cells. Cell Rep. 2019; 27(12):3709-3723.e5. PMC: 6594401. DOI: 10.1016/j.celrep.2019.05.077. View

Cruz N, Reddy R, McFaline-Figueroa J, Tran C, Fu H, Freedman B . Modelling ciliopathy phenotypes in human tissues derived from pluripotent stem cells with genetically ablated cilia. Nat Biomed Eng. 2022; 6(4):463-475. PMC: 9228023. DOI: 10.1038/s41551-022-00880-8. View

Hiratsuka K, Miyoshi T, Kroll K, Gupta N, Valerius M, Ferrante T . Organoid-on-a-chip model of human ARPKD reveals mechanosensing pathomechanisms for drug discovery. Sci Adv. 2022; 8(38):eabq0866. PMC: 9491724. DOI: 10.1126/sciadv.abq0866. View

Zhang S, Wan Z, Kamm R . Vascularized organoids on a chip: strategies for engineering organoids with functional vasculature. Lab Chip. 2021; 21(3):473-488. PMC: 8283929. DOI: 10.1039/d0lc01186j. View

Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T . Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013; 499(7459):481-4. DOI: 10.1038/nature12271. View

Guan Y, Enejder A, Wang M, Fang Z, Cui L, Chen S . A human multi-lineage hepatic organoid model for liver fibrosis. Nat Commun. 2021; 12(1):6138. PMC: 8536785. DOI: 10.1038/s41467-021-26410-9. View

10.

Jacob A, Morley M, Hawkins F, McCauley K, Jean J, Heins H . Differentiation of Human Pluripotent Stem Cells into Functional Lung Alveolar Epithelial Cells. Cell Stem Cell. 2017; 21(4):472-488.e10. PMC: 5755620. DOI: 10.1016/j.stem.2017.08.014. View

11.

Lewis-Israeli Y, Wasserman A, Gabalski M, Volmert B, Ming Y, Ball K . Self-assembling human heart organoids for the modeling of cardiac development and congenital heart disease. Nat Commun. 2021; 12(1):5142. PMC: 8390749. DOI: 10.1038/s41467-021-25329-5. View

12.

Zhou T, Tan L, Cederquist G, Fan Y, Hartley B, Mukherjee S . High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain. Cell Stem Cell. 2017; 21(2):274-283.e5. PMC: 5553280. DOI: 10.1016/j.stem.2017.06.017. View

13.

Hannan N, Segeritz C, Touboul T, Vallier L . Production of hepatocyte-like cells from human pluripotent stem cells. Nat Protoc. 2013; 8(2):430-7. PMC: 3673228. DOI: 10.1038/nprot.2012.153. View

14.

Takahashi K, Yamanaka S . Induction of pluripotent stem cells from mouse embryonic and adult fibroblast cultures by defined factors. Cell. 2006; 126(4):663-76. DOI: 10.1016/j.cell.2006.07.024. View

15.

Vogt N . Assembloids. Nat Methods. 2021; 18(1):27. DOI: 10.1038/s41592-020-01026-x. View

16.

Hernandez J, Wang X, Vazquez-Segoviano M, Lopez-Marfil M, Sobral-Reyes M, Moran-Horowich A . A tissue-bioengineering strategy for modeling rare human kidney diseases in vivo. Nat Commun. 2021; 12(1):6496. PMC: 8586030. DOI: 10.1038/s41467-021-26596-y. View

17.

Lee M, Lee S, Jung C, Son Y, Ryu J, Jung K . Development of a quantitative prediction algorithm for target organ-specific similarity of human pluripotent stem cell-derived organoids and cells. Nat Commun. 2021; 12(1):4492. PMC: 8302568. DOI: 10.1038/s41467-021-24746-w. View

18.

Thomson J, Itskovitz-Eldor J, Shapiro S, Waknitz M, Swiergiel J, Marshall V . Embryonic stem cell lines derived from human blastocysts. Science. 1998; 282(5391):1145-7. DOI: 10.1126/science.282.5391.1145. View

19.

Arzua T, Yan Y, Jiang C, Logan S, Allison R, Wells C . Modeling alcohol-induced neurotoxicity using human induced pluripotent stem cell-derived three-dimensional cerebral organoids. Transl Psychiatry. 2020; 10(1):347. PMC: 7553959. DOI: 10.1038/s41398-020-01029-4. View

20.

Peng C, Trojanowski J, Lee V . Protein transmission in neurodegenerative disease. Nat Rev Neurol. 2020; 16(4):199-212. PMC: 9242841. DOI: 10.1038/s41582-020-0333-7. View