Disease Modelling in Human Organoids

Overview

Journal Dis Model Mech

Specialty General Medicine

Date 2019 Aug 7

PMID 31383635

Citations 169

Authors

Madeline A Lancaster

Meritxell Huch

Affiliations

Soon will be listed here.

Abstract

The past decade has seen an explosion in the field of disease modelling, in particular the development of organoids. These self-organizing tissues derived from stem cells provide a unique system to examine mechanisms ranging from organ development to homeostasis and disease. Because organoids develop according to intrinsic developmental programmes, the resultant tissue morphology recapitulates organ architecture with remarkable fidelity. Furthermore, the fact that these tissues can be derived from human progenitors allows for the study of uniquely human processes and disorders. This article and accompanying poster highlight the currently available methods, particularly those aimed at modelling human biology, and provide an overview of their capabilities and limitations. We also speculate on possible future technological advances that have the potential for great strides in both disease modelling and future regenerative strategies.

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References

van de Wetering M, Francies H, Francis J, Bounova G, Iorio F, Pronk A . Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015; 161(4):933-45. PMC: 6428276. DOI: 10.1016/j.cell.2015.03.053. View

Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P . In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology. 2014; 148(1):126-136.e6. PMC: 4274199. DOI: 10.1053/j.gastro.2014.09.042. View

Parfitt D, Lane A, Ramsden C, Carr A, Munro P, Jovanovic K . Identification and Correction of Mechanisms Underlying Inherited Blindness in Human iPSC-Derived Optic Cups. Cell Stem Cell. 2016; 18(6):769-781. PMC: 4899423. DOI: 10.1016/j.stem.2016.03.021. View

Loomans C, Williams Giuliani N, Balak J, Ringnalda F, van Gurp L, Huch M . Expansion of Adult Human Pancreatic Tissue Yields Organoids Harboring Progenitor Cells with Endocrine Differentiation Potential. Stem Cell Reports. 2018; 10(3):712-724. PMC: 5918840. DOI: 10.1016/j.stemcr.2018.02.005. View

Karzbrun E, Kshirsagar A, Cohen S, Hanna J, Reiner O . Human Brain Organoids on a Chip Reveal the Physics of Folding. Nat Phys. 2018; 14(5):515-522. PMC: 5947782. DOI: 10.1038/s41567-018-0046-7. View

Kuijk E, Rasmussen S, Blokzijl F, Huch M, Gehart H, Toonen P . Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure. Sci Rep. 2016; 6:22154. PMC: 4768167. DOI: 10.1038/srep22154. View

Huch M, Dorrell C, Boj S, van Es J, Li V, van de Wetering M . In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature. 2013; 494(7436):247-50. PMC: 3634804. DOI: 10.1038/nature11826. View

Boretto M, Cox B, Noben M, Hendriks N, Fassbender A, Roose H . Development of organoids from mouse and human endometrium showing endometrial epithelium physiology and long-term expandability. Development. 2017; 144(10):1775-1786. DOI: 10.1242/dev.148478. View

Kimura H, Sakai Y, Fujii T . Organ/body-on-a-chip based on microfluidic technology for drug discovery. Drug Metab Pharmacokinet. 2017; 33(1):43-48. DOI: 10.1016/j.dmpk.2017.11.003. View

10.

Heo I, Dutta D, Schaefer D, Iakobachvili N, Artegiani B, Sachs N . Modelling Cryptosporidium infection in human small intestinal and lung organoids. Nat Microbiol. 2018; 3(7):814-823. PMC: 6027984. DOI: 10.1038/s41564-018-0177-8. View

11.

Jung P, Sato T, Merlos-Suarez A, Barriga F, Iglesias M, Rossell D . Isolation and in vitro expansion of human colonic stem cells. Nat Med. 2011; 17(10):1225-7. DOI: 10.1038/nm.2470. View

12.

Gao D, Vela I, Sboner A, Iaquinta P, Karthaus W, Gopalan A . Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014; 159(1):176-187. PMC: 4237931. DOI: 10.1016/j.cell.2014.08.016. View

13.

Nantasanti S, Spee B, Kruitwagen H, Chen C, Geijsen N, Oosterhoff L . Disease Modeling and Gene Therapy of Copper Storage Disease in Canine Hepatic Organoids. Stem Cell Reports. 2015; 5(5):895-907. PMC: 4649105. DOI: 10.1016/j.stemcr.2015.09.002. View

14.

Saito Y, Onishi N, Takami H, Seishima R, Inoue H, Hirata Y . Development of a functional thyroid model based on an organoid culture system. Biochem Biophys Res Commun. 2018; 497(2):783-789. DOI: 10.1016/j.bbrc.2018.02.154. View

15.

Garcez P, Loiola E, Madeiro da Costa R, Higa L, Trindade P, Delvecchio R . Zika virus impairs growth in human neurospheres and brain organoids. Science. 2016; 352(6287):816-8. DOI: 10.1126/science.aaf6116. View

16.

Huch M, Gehart H, van Boxtel R, Hamer K, Blokzijl F, Verstegen M . Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell. 2014; 160(1-2):299-312. PMC: 4313365. DOI: 10.1016/j.cell.2014.11.050. View

17.

Xin L, Lukacs R, Lawson D, Cheng D, Witte O . Self-renewal and multilineage differentiation in vitro from murine prostate stem cells. Stem Cells. 2007; 25(11):2760-9. DOI: 10.1634/stemcells.2007-0355. View

18.

Zernicka-Goetz M, Hadjantonakis A . From pluripotency to differentiation: laying foundations for the body pattern in the mouse embryo. Philos Trans R Soc Lond B Biol Sci. 2014; 369(1657). PMC: 4216458. DOI: 10.1098/rstb.2013.0535. View

19.

Takebe T, Sekine K, Kimura M, Yoshizawa E, Ayano S, Koido M . Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells. Cell Rep. 2017; 21(10):2661-2670. DOI: 10.1016/j.celrep.2017.11.005. View

20.

Hynds R, Vladimirou E, Janes S . The secret lives of cancer cell lines. Dis Model Mech. 2018; 11(11). PMC: 6262811. DOI: 10.1242/dmm.037366. View