Human enteroids/colonoids and intestinal organoids functionally recapitulate normal intestinal physiology and pathophysiology

Journal of Biological Chemistry

Volumn 291, Issue 8, 2016, Pages 3759-3766

  Zachos, Nicholas C ^a   Kovbasnjuk, Olga ^a   Foulke Abel, Jennifer ^a   In, Julie ^a   Blutt, Sarah E ^a   De Jonge, Hugo R ^b   Estes, Mary K ^a   Donowitz, Mark ^a,c  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b BAYLOR COLLEGE OF MEDICINE   (United States)

^c ERASMUS MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

CELL PROLIFERATION; CELLS; CYTOLOGY; PHYSIOLOGY;

FUTURE APPLICATIONS; GROWTH FACTOR; HOST-PATHOGEN INTERACTIONS; ORGANOIDS; PATHOPHYSIOLOGY; PLURIPOTENT STEM CELLS; PRIMARY CULTURE; REGENERATIVE MEDICINE;

STEM CELLS;

CELL DIFFERENTIATION; CELL SURVIVAL; ENTEROPATHY; HOST PATHOGEN INTERACTION; HUMAN; INTESTINAL STEM CELL; INTESTINE CRYPT; LIFESPAN; NONHUMAN; ONTOGENY; ORGANOGENESIS; PATHOPHYSIOLOGY; PHYSIOLOGICAL PROCESS; PRIORITY JOURNAL; REVIEW; SIGNAL TRANSDUCTION; ADULT STEM CELL; CYTOPLASM; DIARRHEA; INDUCED PLURIPOTENT STEM CELL; INTESTINE; METABOLISM; PATHOLOGY;

DIFFERENTIATION ANTIGEN; G PROTEIN COUPLED RECEPTOR; LGR5 PROTEIN, HUMAN;

ADULT STEM CELLS; ANTIGENS, DIFFERENTIATION; DIARRHEA; HUMANS; INDUCED PLURIPOTENT STEM CELLS; INTESTINES; ORGANOIDS; RECEPTORS, G-PROTEIN-COUPLED;

EID: 85015995278     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.R114.635995     Document Type: Review

References (61)

1. Woodcock, J., and Woosley, R. (2008) The FDA critical path initiative and its influence on new drug development. Annu. Rev. Med. 59, 1-12
2. Barker, N., van Es, J. H., Kuipers, J., Kujala, P., van den Born, M., Cozijnsen, M., Haegebarth, A., Korving, J., Begthel, H., Peters, P. J., and Clevers, H. (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449, 1003-1007
3. Jung, P., Sato, T., Merlos-Suárez, A., Barriga, F. M., Iglesias, M., Rossell, D., Auer, H., Gallardo, M., Blasco, M. A., Sancho, E., Clevers, H., and Batlle, E. (2011) Isolation and in vitro expansion of human colonic stem cells. Nat. Med. 17, 1225-1227
4. Sato, T., and Stange, D. E., Ferrante, M., Vries, R. G., Van Es, J. H., Van den Brink, S., Van Houdt, W. J., Pronk, A., Van Gorp, J., Siersema, P. D., and Clevers, H. (2011) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett's epithelium. Gastroenterology 141, 1762-1772
5. Spence, J. R., and Mayhew, C. N., Rankin, S. A., Kuhar, M. F., and Vallance, J. E., Tolle, K., Hoskins, E. E., and Kalinichenko, V. V., Wells, S. I., Zorn, A. M., and Shroyer, N. F., and Wells, J. M. (2011) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470, 105-109
6. Sato, T., and Clevers, H. (2013) Growing self-organizing mini-guts from a single intestinal stem cell: mechanism and applications. Science 340, 1190-1194
7. Sato, T., and Vries, R. G., Snippert, H. J., van de Wetering, M., Barker, N., and Stange, D. E., van Es, J. H., Abo, A., Kujala, P., Peters, P. J., and Clevers, H. (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459, 262-265
8. Stelzner, M., Helmrath, M., Dunn, J. C, Henning, S.J., and Houchen, C. W., Kuo, C, Lynch, J., Li, L., Magness, S. T., Martin, M. G., Wong, M. H., Yu, J., and the NIH Intestinal Stem Cell Consortium (2012) A nomenclature for intestinal in vitro cultures. Am. J. Physiol. Gastrointest. Liver Physiol. 302, G1359-G1363
9. Foulke-Abel, J., In, J., Kovbasnjuk, O., Zachos, N. C, Ettayebi, K., and Blutt, S. E., Hyser, J. M., Zeng, X. L., and Crawford, S. E., Broughman, J. R., Estes, M. K., and Donowitz, M. (2014) Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract. Exp. Biol. Med. (Maywood) 239, 1124-1134
10. Lancaster, M. A., and Knoblich, J. A. (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345, 1247125
11. Leushacke, M., and Barker, N. (2014) Ex vivo culture of the intestinal epithelium: strategies and applications. Gut 63, 1345-1354
12. Dekkers, J. F., and 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., Bijvelds, M. J., Scholte, B. J., Nieuwenhuis, E. E., van den Brink, S., Clevers, H., van der Ent, C. K., Middendorp, S., and Beekman, J. M. (2013) A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat. Med. 19, 939-945
13. Kovbasnjuk, O., Zachos, N. C, In, J., Foulke-Abel, J., Ettayebi, K., and Hyser, J. M., Broughman, J. R., Zeng, X. L., Middendorp, S., de Jonge, H. R., Estes, M. K., and Donowitz, M. (2013) Human enteroids: preclinical models of non-inflammatory diarrhea. Stem Cell Res. Ther. 4, Suppl. 1, S3
14. Schwank, G., and Koo, B. K., Sasselli, V., Dekkers, J. F., Heo, I., Demircan, T., Sasaki, N, Boymans, S., Cuppen, E., van der Ent, C K., Nieuwenhuis, E. E., Beekman, J. M., and Clevers, H. (2013) Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13, 653-658
15. Spurrier, R. G., and Grikscheit, T. C. (2013) Tissue engineering the small intestine. Clin. Gastroenterol. Hepatol. 11, 354-358
16. VanDussen, K. L., and Marinshaw, J. M., Shaikh, N, Miyoshi, H, Moon, C, and Tarr, P. I., Ciorba, M. A., and Stappenbeck, T. S. (2015) Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Gut 64, 911-920
17. + stem cells require SpiB and are induced by RankL in cultured "miniguts". Mol. Cell. Biol. 32, 3639-3647
18. Yeung, T. M., and Chia, L. A., Kosinski, CM., and Kuo, C.J. (2011) Regulation of self-renewal and differentiation by the intestinal stem cell niche. Cell. Mol. Life Sci. 68, 2513-2523
19. Fordham, R. P., Yui, S., Hannan, N. R., Soendergaard, C, Madgwick, A., and Schweiger, P. J., Nielsen, O. H, Vallier, L., and Pedersen, R. A., Nakamura, T., Watanabe, M., and Jensen, K. B. (2013) Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 13, 734-744
20. Forster, R., Chiba, K., Schaeffer, L., Regalado, S. G., and Lai, C. S., Gao, Q., Kiani, S., Farin, H. F., Clevers, H, and Cost, G. J., Chan, A., Rebar, E. J., and Urnov, F. D., Gregory, P. D., Pachter, L., Jaenisch, R., and Hockemeyer, D. (2014) Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. Stem Cell Reports 2, 838-852
21. Dolnikov, K., Shilkrut, M., Zeevi-Levin, N, Danon, A., Gerecht-Nir, S., Itskovitz-Eldor, J., and Binah, O. (2005) Functional properties of human embryonic stem cell-derived cardiomyocytes. Ann. N.Y. Acad. Sci. 1047, 66-75
22. Kroon, E., and Martinson, L. A., Kadoya, K., Bang, A. G., and Kelly, O. G., Eliazer, S., Young, H., Richardson, M., and Smart, N. G., Cunningham, J., Agulnick, A. D., D'Amour, K. A., Carpenter, M. K., and Baetge, E. E. (2008) Pancreatic endoderm derived from human embryonic stem cells generates glucose-responsive insulin-secreting cells in vivo. Nat. Biotechnol. 26, 443-452
23. Si-Tayeb, K., Noto, F. K., Nagaoka, M., Li, J., Battle, M. A., Duris, C, and North, P. E., Dalton, S., and Duncan, S. A. (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51, 297-305
24. Wong, A. P., and Bear, C. E., Chin, S., Pasceri, P., Thompson, T. O., and Huan, L. J., Ratjen, F., Ellis, J., and Rossant, J. (2012) Directed differentiation of human pluripotent stem cells into mature airway epithelia expressing functional CFTR protein. Nat. Biotechnol. 30, 876-882
25. D'Amour, K. A., Bang, A. G., Eliazer, S., and Kelly, O. G., Agulnick, A. D., Smart, N. G., Moorman, M.A., Kroon, E., and Carpenter, M. K., and Baetge, E. E. (2006) Production of pancreatic hormone-expressing endocrine cells from human embryonic stem cells. Nat. Biotechnol. 24, 1392-1401
26. DeLaForest, A., Nagaoka, M., Si-Tayeb, K., Noto, F. K., Konopka, G., and Battle, M. A., and Duncan, S. A. (2011) HNF4A is essential for specification of hepatic progenitors from human pluripotent stem cells. Development 138, 4143-4153
27. Watson, C. L., and Mahe, M. M., Múnera, J., Howell, J. C, Sundaram, N, and Poling, H. M., Schweitzer, J. I., Vallance, J. E., Mayhew, C. N, Sun, Y., Grabowski, G., Finkbeiner, S. R., Spence, J. R., Shroyer, N. F., Wells, J. M., and Helmrath, M. A. (2014) An in vivo model of human small intestine using pluripotent stem cells. Nat Med. 20, 1310-1314
28. Kim, H. J., Huh, D., Hamilton, G., and Ingber, D. E. (2012) Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsislike motions and flow. Lab Chip 12, 2165-2174
29. Shyer, A. E., Tallinen, T., Nerurkar, N. L., Wei, Z., and Gil, E. S., Kaplan, D. L., Tabin, C. J., and Mahadevan, L. (2013) Villification: how the gut gets its villi. Science 342, 212-218
30. Middendorp, S., Schneeberger, K., Wiegerinck, C. L., Mokry, M., and Akkerman, R. D., van Wijngaarden, S., Clevers, H., and Nieuwenhuis, E. E. (2014) Adult stem cells in the small intestine are intrinsically programmed with their location-specific function. Stem Cells 32, 1083-1091
31. + exchangers NHE2 and NHE3. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G202-G210
32. Foulke-Abel, J., In, J., Zachos, N. C, Kovbasnjuk, O., Ettayebi, K., de Jonge, H. R., Estes, M. K., and Donowitz, M. (2014) Human small intestinal enteroids enable mechanistic studies of cAMP-induced changes in intracellular pH. Gastroenterology 146, A190
33. Ma, T., and Thiagarajah, J. R., Yang, H, and Sonawane, N. D., Folli, C, and Galietta, L. J., and Verkman, A. S. (2002) Thiazolidinone CFTR inhibitor identified by high-throughput screening blocks cholera toxin-induced intestinal fluid secretion. J. Clin. Invest. 110, 1651-1658
34. Muanprasat, C, and Sonawane, N. D., Salinas, D., Taddei, A., Galietta, L. J., and Verkman, A. S. (2004) Discovery of glycine hydrazide pore-occluding CFTR inhibitors: mechanism, structure-activity analysis, and in vivo efficacy. J. Gen. Physiol. 124, 125-137
35. Ikpa, P. T., and Bijvelds, M. J., and de Jonge, H. R. (2014) Cystic fibrosis: toward personalized therapies. Int. J. Biochem. Cell Biol. 52, 192-200
36. Finkbeiner, S. R., and Zeng, X. L., Utama, B., Atmar, R. L., and Shroyer, N. F., and Estes, M. K. (2012) Stem cell-derived human intestinal organoids as an infection model for rotaviruses. MBio 3, e00159-00112
37. Zachos, N. C, Foulke-Abel, J., Biswas, R. S., In, J., Wang, P., Brown, H. A., Kovbasnjuk, O., and Estes, M. K. (2014) Rotavirus inhibits NHE3 activity via clathrin-independent endocytosis resulting in increased NHE3 degradation. Gastroenterology 146, Mo1939
38. In, J., Foulke-Abel, J., Cole, R. N, and Kovbasnjuk, O. (2014) EHEC virulence factor EspP cleaves actin binding protein fodrin to induce macropinocytosis of shiga toxins. Gastroenterology 146, Sa1743
39. Leslie, J. L., Huang, S., Opp, J. S., and Nagy, M. S., Kobayashi, M., Young, V. B., and Spence, J. R. (2015) Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect. Immun. 83, 138-145
40. Engevik, M. A., and Engevik, K. A., Yacyshyn, M. B., Wang, J., Hassett, D. J., Darien, B., and Yacyshyn, B. R., and Worrell, R. T. (2015) Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G497-G509
41. Engevik, M. A., and Yacyshyn, M. B., Engevik, K. A., Wang, J., Darien, B., and Hassett, D. J., Yacyshyn, B. R., and Worrell, R. T. (2015) Human Clostridium difficile infection: altered mucus production and composition. Am. J. Physiol. Gastrointest. Liver Physiol. 308, G510-G524
42. Chandrakesan, P., Roy, B., Jakkula, L. U., Ahmed, I., Ramamoorthy, P., Tawfik, O., Papineni, R., Houchen, C, Anant, S., and Umar, S. (2014) Utility of a bacterial infection model to study epithelial-mesenchymal transition, mesenchymal-epithelial transition or tumorigenesis. Oncogene 33, 2639-2654
43. Miyoshi, H, and Stappenbeck, T. S. (2013) The young and the Wnt-less: transplantable fetal intestinal spheroids without Wnts. Cell Stem Cell 13, 637-638
44. + intestinal stem cells and their progeny. Nat. Methods 11, 106-112
45. Sambuy, Y., De Angelis, I., Ranaldi, G., Scarino, M. L., Stammati, A., and Zucco, F. (2005) The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics. Cell Biol. Toxicol. 21, 1-26
46. Blanpain, C, and Fuchs, E. (2014) Stem cell plasticity. Plasticity of epithelial stem cells in tissue regeneration. Science 344, 1242281
47. Montgomery, R. K., and Carlone, D. L., Richmond, C A., Farilla, L., Kranendonk, M. E., Henderson, D. E., Baffour-Awuah, N. Y., Ambruzs, D. M., Fogli, L. K., Algra, S., and Breault, D. T. (2011) Mouse telomerase reverse transcriptase (mTert) expression marks slowly cycling intestinal stem cells. Proc. Natl. Acad. Sci. U.S.A. 108, 179-184
48. Ritsma, L., and Ellenbroek, S. I., Zomer, A., Snippert, H. J., de Sauvage, F. J., Simons, B. D., Clevers, H., and van Rheenen, J. (2014) Intestinal crypt homeostasis revealed at single-stem-cell level by in vivo live imaging. Nature 507, 362-365
49. Sangiorgi, E., and Capecchi, M. R. (2008) Bmi1 is expressed in vivo in intestinal stem cells. Nat. Genet. 40, 915-920
50. Takeda, N, Jain, R., LeBoeuf, M. R., Wang, Q., and Lu, M. M., and Epstein, J. A. (2011) Interconversion between intestinal stem cell populations in distinct niches. Science 334, 1420-1424
51. Liu, J., and Walker, N. M., Cook, M. T., Ootani, A., and Clarke, L. L. (2012) Functional Cftr in crypt epithelium of organotypic enteroid cultures from murine small intestine. Am. J. Physiol. Cell Physiol. 302, C1492-C1503
52. Lahar, N, and Lei, N. Y., Wang, J., Jabaji, Z., Tung, S. C, Joshi, V., Lewis, M., Stelzner, M., Martín, M. G., and Dunn, J. C (2011) Intestinal subepithelial myofibroblasts support in vitro and in vivo growth of human small intestinal epithelium. PLoS ONE 6, e26898
53. Evans, G. S., Flint, N, and Somers, A. S., Eyden, B., and Potten, C. S. (1992) The development of a method for the preparation of rat intestinal epithelial cell primary cultures. J. Cell Sci. 101, 219-231
54. Vacanti, J. P., and Morse, M. A., Saltzman, W. M., Domb, A. J., Perez-Atayde, A., and Langer, R. (1988) Selective cell transplantation using bioabsorb-able artificial polymers as matrices. J. Pediatr. Surg. 23, 3-9
55. Levin, D. E., and Barthel, E. R., Speer, A. L., Sala, F. G., Hou, X., Torashima, Y., and Grikscheit, T. C. (2013) Human tissue-engineered small intestine forms from postnatal progenitor cells. J. Pediatr Surg. 48, 129-137
56. El-Nachef, W., and Grikscheit, T. (2014) Enteric nervous system cell replacement therapy for Hirschsprung disease: beyond tissue-engineered intestine. Eur. J. Pediatr. Surg. 24, 214-218
57. Schwank, G., Andersson-Rolf, A., Koo, B. K., Sasaki, N, and Clevers, H. (2013) Generation of BAC transgenic epithelial organoids. PLoS ONE 8, e76871
58. 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., Weis, C. A., Nijman, I. J., Monroe, G. R., van Hasselt, P. M., Cutz, E., Klumperman, J., Clevers, H., Nieuwenhuis, E. E., Houwen, R. H., van Haaften, G., Hess, M. W., Huber, L. A., Stapelbroek, J. M., Müller, T., and Middendorp, S. (2014) Loss of syntaxin 3 causes variant microvillus inclusion disease. Gastroenterology 147, 65-68.e10
59. Brugmann, S. A., and Wells, J. M. (2013) Building additional complexity to in vitro-derived intestinal tissues. Stem Cell Res. Ther. 4, Suppl. 1, S1
60. Bouchi, R., and Foo, K. S., Hua, H., Tsuchiya, K., Ohmura, Y., and Sandoval, P. R., Ratner, L. E., Egli, D., Leibel, R. L., and Accili, D. (2014) FOXO1 inhibition yields functional insulin-producing cells in human gut organoid cultures. Nat. Commun. 5, 4242
61. + exchanger regulatory factor 1 (NHERF1) null mice: cAMP inhibition is differentially dependent on NHERF1 and exchange protein directly activated by cAMP in ileum versus proximal tubule. J. Biol. Chem. 282, 25141-25151