Modeling human disease using organotypic cultures

Current Opinion in Cell Biology

Volumn 43, Issue , 2016, Pages 22-29

  Schweiger, Pawel J ^a   Jensen, Kim B ^a  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

CELL CULTURE; CYTOPLASM; DISEASE MODEL; HUMAN; IN VITRO STUDY; PRIORITY JOURNAL; REVIEW; TISSUE LEVEL; ANIMAL; BIOLOGICAL MODEL; DISEASES; PATHOLOGY; PROCEDURES; TISSUE CULTURE TECHNIQUE;

ANIMALS; DISEASE; HUMANS; MODELS, BIOLOGICAL; ORGANOIDS; TISSUE CULTURE TECHNIQUES;

EID: 84979518893     PISSN: 09550674     EISSN: 18790410     Source Type: Journal    
DOI: 10.1016/j.ceb.2016.07.003     Document Type: Review

References (94)

1. Eiraku, M., Watanabe, K., Matsuo-Takasaki, M., Kawada, M., Yonemura, S., Matsumura, M., Wataya, T., Nishiyama, A., Muguruma, K., Sasai, Y., Self-organized formation of polarized cortical tissues from ESCs and its active manipulation by extrinsic signals. Cell Stem Cell 3 (2008), 519–532.
2. Rock, J.R., Onaitis, M.W., Rawlins, E.L., Lu, Y., Clark, C.P., Xue, Y., Randell, S.H., Hogan, B.L.M., Basal cells as stem cells of the mouse trachea and human airway epithelium. Proc Natl Acad Sci U S A 106 (2009), 12771–12775.
3. Sato, T., Vries, R.G., Snippert, H.J., van de Wetering, M., Barker, N., Stange, D.E., van Es, J.H., Abo, A., Kujala, P., Peters, P.J., et al. Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459 (2009), 262–265.
4. Ader, M., Tanaka, E.M., Modeling human development in 3D culture. Curr Opin Cell Biol 31 (2014), 23–28.
5. Fatehullah, A., Tan, S.H., Barker, N., Organoids as an in vitro model of human development and disease. Nat Cell Biol 18 (2016), 246–254.
6. Rookmaaker, M.B., Schutgens, F., Verhaar, M.C., Clevers, H., Development and application of human adult stem or progenitor cell organoids. Nat Rev Nephrol 11 (2015), 546–554.
7. Huch, M., Koo, B.-K., Modeling mouse and human development using organoid cultures. Development 142 (2015), 3113–3125.
8. McCracken, K.W., Catá, E.M., Crawford, C.M., Sinagoga, K.L., Schumacher, M., Rockich, B.E., Tsai, Y.-H., Mayhew, C.N., Spence, J.R., Zavros, Y., et al. Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516 (2014), 400–404 Authors used human PSCs-derived gastric organoids to investigate the stimulatory effect of H. pylori infections on proliferation of gastric epithelial cells. Bacterial virulence factor (CagA) has been found to rapidly associate with cMet receptor and induce proliferation of gastric epithelium.
9. Bertaux-Skeirik, N., Feng, R., Schumacher, M.A., Li, J., Mahe, M.M., Engevik, A.C., Javier, J.E., Peek, R.M., Ottemann, K., Orian-Rousseau, V., et al. CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation. PLoS Pathog, 11, 2015, e1004663.
10. Bartfeld, S., Bayram, T., van de Wetering, M., Huch, M., Begthel, H., Kujala, P., Vries, R., Peters, P.J., Clevers, H., In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148 (2015), 126–136 Authors observed a significant activation of inflammatory response, including activation of NFk-B, upon H. pylori infections of human SSCs-derived gastric organoids. They identified gastric glands, as opposed to gastric pit, as the compartment predominantly responsible for this reaction.
11. Schumacher, M.A., Feng, R., Aihara, E., Engevik, A.C., Montrose, M.H., Ottemann, K.M., Zavros, Y., Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFκB pathway activation: the use of a novel in vitro model to study epithelial response to infection. Helicobacter 20 (2015), 19–28.
12. Wroblewski, L.E., Piazuelo, M.B., Chaturvedi, R., Schumacher, M., Aihara, E., Feng, R., Noto, J.M., Delgado, A., Israel, D.A., Zavros, Y., et al. Helicobacter pylori targets cancer-associated apical-junctional constituents in gastroids and gastric epithelial cells. Gut 64 (2015), 720–730 Authors used mouse SSCs-derived gastric organoids to show that co-cultures of H. pylori disrupt components of tight junctions and induce beta-catenin signalling. This might explain carcinogenic potential of H. pylori infections.
13. Engevik, M.A., Yacyshyn, M.B., Engevik, K.A., Wang, J., Darien, B., Hassett, D.J., Yacyshyn, B.R., Worrell, R.T., Human Clostridium difficile infection: altered mucus production and composition. Am J Physiol Gastrointest Liver Physiol 308 (2015), G510–G524.
14. Leslie, J.L., Huang, S., Opp, J.S., Nagy, M.S., Kobayashi, M., Young, V.B., Spence, J.R., Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect Immun 83 (2015), 138–145.
15. Wang, X., Yamamoto, Y., Wilson, L.H., Zhang, T., Howitt, B.E., Farrow, M.A., Kern, F., Ning, G., Hong, Y., Khor, C.C., et al. Cloning and variation of ground state intestinal stem cells. Nature 522 (2015), 173–178 Authors derived air-liquid interface organoids from human embryonic SSCs and maintained at clonogenic ‘ground state’ to be sensitive to bacterial toxins (TcdA and TcdB) resulting in loss of differentiation and polarity as well as barrier function.
16. Zhang, Y.-G., Wu, S., Xia, Y., Sun, J., Salmonella-infected crypt-derived intestinal organoid culture system for host-bacterial interactions. Physiol Rep, 2, 2014.
17. Wilson, S.S., Tocchi, A., Holly, M.K., Parks, W.C., Smith, J.G., A small intestinal organoid model of non-invasive enteric pathogen-epithelial cell interactions. Mucosal Immunol 8 (2015), 352–361.
18. Forbester, J.L., Goulding, D., Vallier, L., Hannan, N., Hale, C., Pickard, D., Mukhopadhyay, S., Dougan, G., Interaction of Salmonella enterica Serovar Typhimurium with intestinal organoids derived from human induced pluripotent stem cells. Infect Immun 83 (2015), 2926–2934.
19. Nigro, G., Rossi, R., Commere, P.-H., Jay, P., Sansonetti, P.J., The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15 (2014), 792–798.
20. Lukovac, S., Belzer, C., Pellis, L., Keijser, B.J., de Vos, W.M., Montijn, R.C., Roeselers, G., Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. mBio 5 (2014), e01438–e1514.
21. Finkbeiner, S.R., Zeng, X.-L., Utama, B., Atmar, R.L., Shroyer, N.F., Estes, M.K., Stem cell-derived human intestinal organoids as an infection model for rotaviruses. MBio, 3, 2012 e00159-112.
22. Garcez, P.P., Loiola, E.C., Madeiro da Costa, R., Higa, L.M., Trindade, P., Delvecchio, R., Nascimento, J.M., Brindeiro, R., Tanuri, A., Rehen, S.K., Zika virus impairs growth in human neurospheres and brain organoids. Science 352 (2016), 816–818 Authors used iPSCs-derived human neurospheres and cerebral organoids to show that Zika virus targets human brain cells, reducing their viability and growth.
23. Huch, M., Gehart, H., van Boxtel, R., Hamer, K., Blokzijl, F., Verstegen, M.M.A., Ellis, E., van Wenum, M., Fuchs, S.A., de Ligt, J., et al. Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160 (2015), 299–312 Authors derived organoids from two distinct liver syndromes. In organoids from α1-antitrypsin deficiency patients aggregation of protein in the ER of hepatocytes resembled in vivo phenotype. Cultures from Alagille syndrome patients failed to up-regulate expected markers upon differentiation and instead underwent apoptosis consistent with the patient phenotypes.
24. Behjati, S., Huch, M., van Boxtel, R., Karthaus, W., Wedge, D.C., Tamuri, A.U., Martincorena, I., Petljak, M., Alexandrov, L.B., Gundem, G., et al. Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513 (2014), 422–425.
25. Bigorgne, A.E., Farin, H.F., Lemoine, R., Mahlaoui, N., Lambert, N., Gil, M., Schulz, A., Philippet, P., Schlesser, P., Abrahamsen, T.G., et al. TTC7A mutations disrupt intestinal epithelial apicobasal polarity. J Clin Invest 124 (2014), 328–337 Authors derived intestinal organoids from patients with atresia/combined immunodeficiency (MIA-CID). Observed phenotype is consistent with abnormal intestinal function in MIA-CID patients. TTC7A mutations were identified as a causative factor and linked them to disruption of RHO kinase pathway. Addition of ROCK inhibitor normalized the phenotype observed in 3D organoids.
26. Dekkers, J.F., Wiegerinck, C.L., de Jonge, H.R., Bronsveld, I., Janssens, H.M., de Winter-de Groot, K.M., Brandsma, A.M., de Jong, N.W.M., Bijvelds, M.J.C., Scholte, B.J., et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med 19 (2013), 939–945.
27. Lancaster, M.A., Renner, M., Martin, C.-A., Wenzel, D., Bicknell, L.S., Hurles, M.E., Homfray, T., Penninger, J.M., Jackson, A.P., Knoblich, J.A., Cerebral organoids model human brain development and microcephaly. Nature 501 (2013), 373–379.
28. Mariani, J., Coppola, G., Zhang, P., Abyzov, A., Provini, L., Tomasini, L., Amenduni, M., Szekely, A., Palejev, D., Wilson, M., et al. FOXG1-dependent dysregulation of GABA/glutamate neuron differentiation in autism spectrum disorders. Cell 162 (2015), 375–390.
29. Takasato, M., Er, P.X., Becroft, M., Vanslambrouck, J.M., Stanley, E.G., Elefanty, A.G., Little, M.H., Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat Cell Biol 16 (2014), 118–126.
30. Zhong, X., Gutierrez, C., Xue, T., Hampton, C., Vergara, M.N., Cao, L.-H., Peters, A., Park, T.S., Zambidis, E.T., Meyer, J.S., et al. Generation of three-dimensional retinal tissue with functional photoreceptors from human iPSCs. Nat Commun, 5, 2014, 4047.
31. Drost, J., van Jaarsveld, R.H., Ponsioen, B., Zimberlin, C., van Boxtel, R., Buijs, A., Sachs, N., Overmeer, R.M., Offerhaus, G.J., Begthel, H., et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature 521 (2015), 43–47 Authors used CRISPR-Cas9 system to develop human intestinal organoids containing different combinations of APC, TP53, KRAS and SMAD4 mutations. Mutants in all 4 genes grew self-sufficiently and formed solid tumors upon subcutaneous grafting. Only APC and TP53 mutations were required to induce extensive aneuploidy.
32. Matano, M., Date, S., Shimokawa, M., Takano, A., Fujii, M., Ohta, Y., Watanabe, T., Kanai, T., Sato, T., Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med 21 (2015), 256–262 Authors used CRISPR-Cas9 to develop human colonic organoids containing different combinations of APC, SMAD4, TP53, KRAS and PI3KCA mutations. Mutants in all 5 genes were transcriptionally similar to organoids obtained from human colon adenomas. However, they formed tumors with lower efficiency than colorectal adenocarcinoma organoids when grafted. Only engineered chromosomally-instable patient-derived adenomas were able to form macrometatases upon grafting.
33. Nadauld, L.D., Garcia, S., Natsoulis, G., Bell, J.M., Miotke, L., Hopmans, E.S., Xu, H., Pai, R.K., Palm, C., Regan, J.F., et al. Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer. Genome Biol, 15, 2014, 428 Authors derived mouse gastric organoids harboring mutations in Cdh1 and Trp53 and knock-down of Tgfbr2 using air-liquid interface method. Knock down of Tgfbr2 was required to induce phenotypes of highly invasive diffused gastric cancer.
34. Wang, K., Yuen, S.T., Xu, J., Lee, S.P., Yan, H.H.N., Shi, S.T., Siu, H.C., Deng, S., Chu, K.M., Law, S., et al. Whole-genome sequencing and comprehensive molecular profiling identify new driver mutations in gastric cancer. Nat Genet 46 (2014), 573–582 In a genetic screen of gastric cancer, authors identified several new commonly mutated genes. Mutations in RHOA were detected in almost 15% of adenocarcinomas. RHOA mutant organoids displayed significantly increased 3D organoid formation assays.
35. Weeber, F., van de Wetering, M., Hoogstraat, M., Dijkstra, K.K., Krijgsman, O., Kuilman, T., Gadellaa-van Hooijdonk, C.G.M., van der Velden, D.L., Peeper, D.S., Cuppen, E.P.J.G., et al. Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases. Proc Natl Acad Sci U S A 112 (2015), 13308–13311 Authors derived organoids from tumor biopsies obtained from metastatic colorectal cancer patients. By sequencing around 2000 genes the authors were able to show high levels of correlation between organoids and source biopsy material, indicating that CRC organoids faithfully represent original tumors.
36. van de Wetering, M., Francies, H.E., Francis, J.M., Bounova, G., Iorio, F., Pronk, A., van Houdt, W., van Gorp, J., Taylor-Weiner, A., Kester, L., et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161 (2015), 933–945 Authors established tumor organoid cultures from 20 colorectal carcinoma patients starting a prospective biobank of primary 3D cancer organoid lines. These lines have been sequenced and screened for chemosensitivity using a library of 83 drugs.
37. Baker, L.A., Tiriac, H., Clevers, H., Tuveson, D.A., Modeling pancreatic cancer with organoids. Trends Cancer 2 (2016), 176–190.
38. Gjorevski, N., Ranga, A., Lutolf, M.P., Bioengineering approaches to guide stem cell-based organogenesis. Development 141 (2014), 1794–1804.
39. Nozaki, K., Mochizuki, W., Matsumoto, Y., Matsumoto, T., Fukuda, M., Mizutani, T., Watanabe, M., Nakamura, T., Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes. J Gastroenterol 51 (2016), 206–213.
40. Zhao, C.-M., Hayakawa, Y., Kodama, Y., Muthupalani, S., Westphalen, C.B., Andersen, G.T., Flatberg, A., Johannessen, H., Friedman, R.A., Renz, B.W., et al. Denervation suppresses gastric tumorigenesis. Sci Transl Med, 6, 2014 250ra115.
41. + stem cell. Nat Med 18 (2012), 618–623.
42. Fordham, R.P., Yui, S., Hannan, N.R.F., Soendergaard, C., Madgwick, A., Schweiger, P.J., Nielsen, O.H., Vallier, L., Pedersen, R.A., Nakamura, T., et al. Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 13 (2013), 734–744.
43. Fukuda, M., Mizutani, T., Mochizuki, W., Matsumoto, T., Nozaki, K., Sakamaki, Y., Ichinose, S., Okada, Y., Tanaka, T., Watanabe, M., et al. Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes Dev 28 (2014), 1752–1757.
44. Huch, M., Dorrell, C., Boj, S.F., van Es, J.H., Li, V.S.W., van de Wetering, M., Sato, T., Hamer, K., Sasaki, N., Finegold, M.J., et al. In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494 (2013), 247–250.
45. Huch, M., Bonfanti, P., Boj, S.F., Sato, T., Loomans, C.J.M., van de Wetering, M., Sojoodi, M., Li, V.S.W., Schuijers, J., Gracanin, A., et al. Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J 32 (2013), 2708–2721.
46. Gallico, G.G., O'Connor, N.E., Compton, C.C., Kehinde, O., Green, H., Permanent coverage of large burn wounds with autologous cultured human epithelium. N Engl J Med 311 (1984), 448–451.
47. Schwank, G., Koo, B.-K., Sasselli, V., Dekkers, J.F., Heo, I., Demircan, T., Sasaki, N., Boymans, S., Cuppen, E., van der Ent, C.K., et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13 (2013), 653–658 Authors use CRISPR/Cas9 system to target the CFTR locus and correct F508 mutation characteristic for cystic fibrosis patients using homologous recombination in cultured intestinal stem cells. The corrected allele is fully functional in clonally expanded organoids.
48. Ogawa, M., Ogawa, S., Bear, C.E., Ahmadi, S., Chin, S., Li, B., Grompe, M., Keller, G., Kamath, B.M., Ghanekar, A., Directed differentiation of cholangiocytes from human pluripotent stem cells. Nat Biotechnol 33 (2015), 853–861.
49. Sampaziotis, F., Cardoso de Brito, M., Madrigal, P., Bertero, A., Saeb-Parsy, K., Soares, F.A.C., Schrumpf, E., Melum, E., Karlsen, T.H., Bradley, J.A., et al. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nat Biotechnol 33 (2015), 845–852.
50. Kadoshima, T., Sakaguchi, H., Nakano, T., Soen, M., Ando, S., Eiraku, M., Sasai, Y., Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc Natl Acad Sci U S A 110 (2013), 20284–20289.
51. Pasca, A.M., Sloan, S.A., Clarke, L.E., Tian, Y., Makinson, C.D., Huber, N., Kim, C.H., Park, J.-Y., O'Rourke, N.A., Nguyen, K.D., et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods 12 (2015), 671–678.
52. Jung, P., Sato, T., Merlos-Suárez, A., Barriga, F.M., Iglesias, M., Rossell, D., Auer, H., Gallardo, M., Blasco, M.A., Sancho, E., et al. Isolation and in vitro expansion of human colonic stem cells. Nat Med 17 (2011), 1225–1227.
53. Yin, X., Farin, H.F., van Es, J.H., Clevers, H., Langer, R., Karp, J.M., Niche-independent high-purity cultures of Lgr5+ intestinal stem cells and their progeny. Nat Methods 11 (2014), 106–112.
54. Li, X., Nadauld, L., Ootani, A., Corney, D.C., Pai, R.K., Gevaert, O., Cantrell, M.A., Rack, P.G., Neal, J.T., Chan, C.W.-M., et al. Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat Med 20 (2014), 769–777 Authors derived organoids containing mixed populations of epithelial and mesenchymal cells from mouse colon, stomach and pancreas using air-liquid interface method. By sourcing tissues from transgenic mouse lines authors engineer mutations in Kras, p53, Apc and Smad4. Pancreatic and gastric organoids required only Kras and p53 mutations to form adenocarcinoma upon grafting. Colonic organoids required all 4 mutations to form invasive adenocarcinomas.
55. Watson, C.L., Mahe, M.M., Múnera, J., Howell, J.C., Sundaram, N., Poling, H.M., Schweitzer, J.I., Vallance, J.E., Mayhew, C.N., Sun, Y., et al. An in vivo model of human small intestine using pluripotent stem cells. Nat Med 20 (2014), 1310–1314.
56. Eiraku, M., Takata, N., Ishibashi, H., Kawada, M., Sakakura, E., Okuda, S., Sekiguchi, K., Adachi, T., Sasai, Y., Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472 (2011), 51–56.
57. Nakano, T., Ando, S., Takata, N., Kawada, M., Muguruma, K., Sekiguchi, K., Saito, K., Yonemura, S., Eiraku, M., Sasai, Y., Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10 (2012), 771–785.
58. Gonzalez-Cordero, A., West, E.L., Pearson, R.A., Duran, Y., Carvalho, L.S., Chu, C.J., Naeem, A., Blackford, S.J.I., Georgiadis, A., Lakowski, J., et al. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina. Nat Biotechnol 31 (2013), 741–747.
59. Kuwahara, A., Ozone, C., Nakano, T., Saito, K., Eiraku, M., Sasai, Y., Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat Commun, 6, 2015, 6286.
60. Völkner, M., Zschätzsch, M., Rostovskaya, M., Overall, R.W., Busskamp, V., Anastassiadis, K., Karl, M.O., Retinal organoids from pluripotent stem cells efficiently recapitulate retinogenesis. Stem Cell Rep 6 (2016), 525–538.
61. Koehler, K.R., Mikosz, A.M., Molosh, A.I., Patel, D., Hashino, E., Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature 500 (2013), 217–221.
62. Morizane, R., Lam, A.Q., Freedman, B.S., Kishi, S., Valerius, M.T., Bonventre, J.V., Nephron organoids derived from human pluripotent stem cells model kidney development and injury. Nat Biotechnol 33 (2015), 1193–1200.
63. Freedman, B.S., Brooks, C.R., Lam, A.Q., Fu, H., Morizane, R., Agrawal, V., Saad, A.F., Li, M.K., Hughes, M.R., Werff, R.V., et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun, 6, 2015, 8715.
64. Takebe, T., Sekine, K., Enomura, M., Koike, H., Kimura, M., Ogaeri, T., Zhang, R.-R., Ueno, Y., Zheng, Y.-W., Koike, N., et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499 (2013), 481–484.
65. Guye, P., Ebrahimkhani, M.R., Kipniss, N., Velazquez, J.J., Schoenfeld, E., Kiani, S., Griffith, L.G., Weiss, R., Genetically engineering self-organization of human pluripotent stem cells into a liver bud-like tissue using Gata6. Nat Commun, 7, 2016, 10243.
66. Lee, J.-H., Bhang, D.H., Beede, A., Huang, T.L., Stripp, B.R., Bloch, K.D., Wagers, A.J., Tseng, Y.-H., Ryeom, S., Kim, C.F., Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 156 (2014), 440–455.
67. Dye, B.R., Hill, D.R., Ferguson, M.A.H., Tsai, Y.-H., Nagy, M.S., Dyal, R., Wells, J.M., Mayhew, C.N., Nattiv, R., Klein, O.D., et al. In vitro generation of human pluripotent stem cell derived lung organoids. Elife, 4, 2015, 05098.
68. Konishi, S., Gotoh, S., Tateishi, K., Yamamoto, Y., Korogi, Y., Nagasaki, T., Matsumoto, H., Muro, S., Hirai, T., Ito, I., et al. Directed induction of functional multi-ciliated cells in proximal airway epithelial spheroids from human pluripotent stem cells. Stem Cell Rep 6 (2016), 18–25.
69. Sato, T., Stange, D.E., Ferrante, M., Vries, R.G.J., Van Es, J.H., Van den Brink, S., Van Houdt, W.J., Pronk, A., Van Gorp, J., Siersema, P.D., et al. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141 (2011), 1762–1772.
70. DeWard, A.D., Cramer, J., Lagasse, E., Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 9 (2014), 701–711.
71. Kessler, M., Hoffmann, K., Brinkmann, V., Thieck, O., Jackisch, S., Toelle, B., Berger, H., Mollenkopf, H.-J., Mangler, M., Sehouli, J., et al. The Notch and Wnt pathways regulate stemness and differentiation in human fallopian tube organoids. Nat Commun, 6, 2015, 8989.
72. Boj, S.F., Hwang, C.-I., Baker, L.A., Chio, I.I.C., Engle, D.D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M.S., et al. Organoid models of human and mouse ductal pancreatic cancer. Cell 160 (2015), 324–338 Authors derived mouse and human normal pancreatic organoids. By analyzing tissue from mutant Kras mouse line, authors show that on its own this mutation was sufficient to generate neoplasms resembling pancreatic ductal adenoma and able to metastasize in vivo.
73. Suga, H., Kadoshima, T., Minaguchi, M., Ohgushi, M., Soen, M., Nakano, T., Takata, N., Wataya, T., Muguruma, K., Miyoshi, H., et al. Self-formation of functional adenohypophysis in three-dimensional culture. Nature 480 (2011), 57–62.
74. Karthaus, W.R., Iaquinta, P.J., Drost, J., Gracanin, A., van Boxtel, R., Wongvipat, J., Dowling, C.M., Gao, D., Begthel, H., Sachs, N., et al. Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 159 (2014), 163–175.
75. Chua, C.W., Shibata, M., Lei, M., Toivanen, R., Barlow, L.J., Bergren, S.K., Badani, K.K., McKiernan, J.M., Benson, M.C., Hibshoosh, H., et al. Single luminal epithelial progenitors can generate prostate organoids in culture. Nat Cell Biol 16 (2014), 951–961 1-4. Authors developed organoids from a specific population of mouse prostate cells, castration-resistant Nkx3.1-expressing cells. Upon loss of Pten and acquisition of KRAS mutation resulting organoids displayed disrupted morphology and significantly increased clonogenicity in 3D organoid formation assays.
76. Nanduri, L.S.Y., Baanstra, M., Faber, H., Rocchi, C., Zwart, E., de Haan, G., van Os, R., Coppes, R.P., Purification and ex vivo expansion of fully functional salivary gland stem cells. Stem Cell Rep 3 (2014), 957–964.
77. Maimets, M., Rocchi, C., Bron, R., Pringle, S., Kuipers, J., Giepmans, B.N.G., Vries, R.G.J., Clevers, H., de Haan, G., van Os, R., et al. Long-term in vitro expansion of salivary gland stem cells driven by Wnt signals. Stem Cell Rep 6 (2016), 150–162.
78. Ootani, A., Li, X., Sangiorgi, E., Ho, Q.T., Ueno, H., Toda, S., Sugihara, H., Fujimoto, K., Weissman, I.L., Capecchi, M.R., et al. Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med 15 (2009), 701–706.
79. Spence, J.R., Mayhew, C.N., Rankin, S.A., Kuhar, M.F., Vallance, J.E., Tolle, K., Hoskins, E.E., Kalinichenko, V.V., Wells, S.I., Zorn, A.M., et al. Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470 (2011), 105–109.
80. Barker, N., Huch, M., Kujala, P., van de Wetering, M., Snippert, H.J., van Es, J.H., Sato, T., Stange, D.E., Begthel, H., van den Born, M., et al. Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6 (2010), 25–36.
81. Stange, D.E., Koo, B.-K., Huch, M., Sibbel, G., Basak, O., Lyubimova, A., Kujala, P., Bartfeld, S., Koster, J., Geahlen, J.H., et al. Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155 (2013), 357–368.
82. Noguchi, T.K., Ninomiya, N., Sekine, M., Komazaki, S., Wang, P.-C., Asashima, M., Kurisaki, A., Generation of stomach tissue from mouse embryonic stem cells. Nat Cell Biol 17 (2015), 984–993.
83. Hisha, H., Tanaka, T., Kanno, S., Tokuyama, Y., Komai, Y., Ohe, S., Yanai, H., Omachi, T., Ueno, H., Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells. Sci Rep, 3, 2013, 3224.
84. Ren, W., Lewandowski, B.C., Watson, J., Aihara, E., Iwatsuki, K., Bachmanov, A.A., Margolskee, R.F., Jiang, P., Single Lgr5- or Lgr6-expressing taste stem/progenitor cells generate taste bud cells ex vivo. Proc Natl Acad Sci U S A 111 (2014), 16401–16406.
85. Antonica, F., Kasprzyk, D.F., Opitz, R., Iacovino, M., Liao, X.-H., Dumitrescu, A.M., Refetoff, S., Peremans, K., Manto, M., Kyba, M., et al. Generation of functional thyroid from embryonic stem cells. Nature 491 (2012), 66–71.
86. Kurmann, A.A., Serra, M., Hawkins, F., Rankin, S.A., Mori, M., Astapova, I., Ullas, S., Lin, S., Bilodeau, M., Rossant, J., et al. Regeneration of thyroid function by transplantation of differentiated pluripotent stem cells. Cell Stem Cell 17 (2015), 527–542.
87. Wiegerinck, C.L., Janecke, A.R., Schneeberger, K., Vogel, G.F., van Haaften-Visser, D.Y., Escher, J.C., Adam, R., Thöni, C.E., Pfaller, K., Jordan, A.J., et al. Loss of syntaxin 3 causes variant microvillus inclusion disease. Gastroenterology 147 (2014), 65–68.
88. Dow, L.E., O'Rourke, K.P., Simon, J., Tschaharganeh, D.F., van Es, J.H., Clevers, H., Lowe, S.W., Apc restoration promotes cellular differentiation and reestablishes crypt homeostasis in colorectal cancer. Cell 161 (2015), 1539–1552.
89. Huang, L., Holtzinger, A., Jagan, I., BeGora, M., Lohse, I., Ngai, N., Nostro, C., Wang, R., Muthuswamy, L.B., Crawford, H.C., et al. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell- and patient-derived tumor organoids. Nat Med 21 (2015), 1364–1371 Authors developed a novel model of primary human pancreatic adenocarcinoma by direct differentiation of PSCs into exocrine progenitor organoids. Upon transduction with KRAS and dominant negative TP53, organoids acquire adenocarcinoma like properties. Authors also derive cancer organoids form cancer patients and characterize their specific sensitivities to novel therapeutic agents.
90. Walsh, A.J., Castellanos, J.A., Nagathihalli, N.S., Merchant, N.B., Skala, M.C., Optical imaging of drug-induced metabolism changes in murine and human pancreatic cancer organoids reveals heterogeneous drug response. Pancreas, 2015, 10.1097/MPA.0000000000000543.
91. Gao, D., Vela, I., Sboner, A., Iaquinta, P.J., Karthaus, W.R., Gopalan, A., Dowling, C., Wanjala, J.N., Undvall, E.A., Arora, V.K., et al. Organoid cultures derived from patients with advanced prostate cancer. Cell 159 (2014), 176–187 Authors developed 3D organoid cultures derived from patients with advanced prostate cancer biopsies and circulating tumor cells. 3D cultures resemble primary tumors histologically and genetically.
92. Park, J.W., Lee, J.K., Phillips, J.W., Huang, P., Cheng, D., Huang, J., Witte, O.N., Prostate epithelial cell of origin determines cancer differentiation state in an organoid transformation assay. Proc Natl Acad Sci U S A 113 (2016), 4482–4487.
93. Hubert, C.G., Rivera, M., Spangler, L.C., Wu, Q., Mack, S.C., Prager, B.C., Couce, M., McLendon, R.E., Sloan, A.E., Rich, J.N., A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo. Cancer Res 76 (2016), 2465–2477.
94. Endo, H., Okami, J., Okuyama, H., Kumagai, T., Uchida, J., Kondo, J., Takehara, T., Nishizawa, Y., Imamura, F., Higashiyama, M., et al. Spheroid culture of primary lung cancer cells with neuregulin 1/HER3 pathway activation. J Thorac Oncol 8 (2013), 131–139.