Human Gastrointestinal Organoid Models for Studying Microbial Disease and Cancer

Chakrabarti, Jayati; Dua-Awereh, Martha B.; Holokai, Loryn; Zavros, Yana

doi:10.1007/82_2020_223

Jayati Chakrabarti¹²,
Martha B. Dua-Awereh¹³,
Loryn Holokai¹⁴ &
…
Yana Zavros¹²

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 430))

1102 Accesses
1 Citations

Abstract

One of the major discoveries in stem cell research in the past decade embraces the development of “organs in a dish,” also known as “organoids.” Organoids are three-dimensional cellular structures derived from primary stem cells of different organ-specific cell types which are capable of self-renewal and maintenance of the parental lineages. Researchers have developed in vitro organoid models to mimic in vivo host–microbial interactions and disease. In this review, we focus on the use of gastrointestinal organoids as models of microbial disease and cancer.

Jayati Chakrabarti, Martha B. Dua-Awereh—Equal contribution.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Chapter: USD 29.95; Price excludes VAT (USA)

eBook: USD 119.00; Price excludes VAT (USA)

Softcover Book: USD 159.99; Price excludes VAT (USA)

Hardcover Book: USD 159.99; Price excludes VAT (USA)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

3D:: Three dimensional
iPSC:: Induced pluripotent stem cell
ESC:: Embryonic stem cell
GI:: Gastrointestinal
Lgr5:: Leucine-rich repeat-containing G-protein-coupled receptor 5
HuNoV:: Human norovirus
ZIKV:: Zika virus
SPEM:: Spasmolytic polypeptide expressing metaplasia
PBMCs:: Peripheral blood mononuclear cells
DCs:: Dendritic cells
TCL:: Tumor cell lysate
CD:: Cluster of differentiation
MHC:: Major histocompatibility complex
IEL:: Intraepithelial lymphocytes
CTLA4:: Cytotoxic T lymphocyte-associated protein 4
PD-1:: Program death 1
PD-L1:: Program death ligand 1
RCC:: Renal cell carcinoma
ATB:: Ampicillin, colistin, and streptomycin
TME:: Tumor microenvironment
CagA:: Cytotoxin-associated gene A
TFF2:: Trefoil factor 2
PMN-MDSCs:: Polymorphonuclear myeloid-derived suppressor cells
Slfn:: Schlafen
VEGF:: Vascular endothelial growth factor
TNFα:: Tumor necrosis factor α
IL-1β:: Interleukin 1β
Treg:: Regulatory T cell
IL-2:: Interleukin 2
ALI:: Air–liquid interface
Th1/2:: T helper cell ½

References

Barker N, Huch M, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M, Danenberg E, van den Brink S, Korving J, Abo A, Peters PJ, Wright N, Poulsom R, Clevers H (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6(1):25–36. https://doi.org/10.1016/j.stem.2009.11.013
Article CAS PubMed Google Scholar
Bartfeld S, Bayram T, van de Wetering M, Huch M, Begthel H, Kujala P, Vries R, Peters PJ, Clevers H (2015) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148(1):126–136.e126. https://doi.org/10.1053/j.gastro.2014.09.042
Article PubMed Google Scholar
Bertaux-Skeirik N, Feng R, Schumacher MA, Li J, Mahe MM, Engevik AC, Javier JE, Peek RM Jr, Ottemann K, Orian-Rousseau V, Boivin GP, Helmrath MA, Zavros Y (2015) CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation. PLoS Pathog 11(2):e1004663. https://doi.org/10.1371/journal.ppat.1004663
Article CAS PubMed PubMed Central Google Scholar
Bertaux-Skeirik N, Wunderlich M, Teal E, Chakrabarti J, Biesiada J, Mahe M, Sundaram N, Gabre J, Hawkins J, Jian G, Engevik AC, Yang L, Wang J, Goldenring JR, Qualls JE, Medvedovic M, Helmrath MA, Diwan T, Mulloy JC, Zavros Y (2017) CD44 variant isoform 9 emerges in response to injury and contributes to the regeneration of the gastric epithelium. J Pathol 242(4):463–475. https://doi.org/10.1002/path.4918
Article CAS PubMed PubMed Central Google Scholar
Boj SF, Hwang CI, Baker LA, Chio II, Engle DD, Corbo V, Jager M, Ponz-Sarvise M, Tiriac H, Spector MS, Gracanin A, Oni T, Yu KH, van Boxtel R, Huch M, Rivera KD, Wilson JP, Feigin ME, Öhlund D, Handly-Santana A, Ardito-Abraham CM, Ludwig M, Elyada E, Alagesan B, Biffi G, Yordanov GN, Delcuze B, Creighton B, Wright K, Park Y, Morsink FH, Molenaar IQ, Borel Rinkes IH, Cuppen E, Hao Y, Jin Y, Nijman IJ, Iacobuzio-Donahue C, Leach SD, Pappin DJ, Hammell M, Klimstra DS, Basturk O, Hruban RH, Offerhaus GJ, Vries RG, Clevers H, Tuveson DA (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160(1–2):324–338. https://doi.org/10.1016/j.cell.2014.12.021
Article CAS PubMed Google Scholar
Chakrabarti J, Holokai L, Syu L, Steele N, Chang J, Dlugosz A, Zavros Y (2018a) Mouse-derived gastric organoid and immune cell co-culture for the study of the tumor microenvironment. Methods Mol Biol 1817:157–168. https://doi.org/10.1007/978-1-4939-8600-2_16
Article CAS PubMed Google Scholar
Chakrabarti J, Holokai L, Syu L, Steele NG, Chang J, Wang J, Ahmed S, Dlugosz A, Zavros Y (2018b) Hedgehog signaling induces PD-L1 expression and tumor cell proliferation in gastric cancer. Oncotarget 9(100):37439–37457. https://doi.org/10.18632/oncotarget.26473
Article PubMed PubMed Central Google Scholar
Chen HN, Wang Z, Li X, Zhou ZG (2016) Helicobacter pylori eradication cannot reduce the risk of gastric cancer in patients with intestinal metaplasia and dysplasia: evidence from a meta-analysis. Gastric Cancer 19(1):166–175. https://doi.org/10.1007/s10120-015-0462-7
Article PubMed Google Scholar
Cohn L, Delamarre L (2014) Dendritic cell-targeted vaccines. Front Immunol 5:255. https://doi.org/10.3389/fimmu.2014.00255
Article CAS PubMed PubMed Central Google Scholar
Dang J, Tiwari SK, Lichinchi G, Qin Y, Patil VS, Eroshkin AM, Rana TM (2016) Zika virus depletes neural progenitors in human cerebral organoids through activation of the innate immune receptor TLR3. Cell Stem Cell 19(2):258–265. https://doi.org/10.1016/j.stem.2016.04.014
Article CAS PubMed PubMed Central Google Scholar
Dang JW, Tiwari SK, Qin Y, Rana TM (2019) Genome-wide Integrative Analysis of Zika-Virus-Infected Neuronal Stem Cells Reveals Roles for MicroRNAs in Cell Cycle and Stemness. Cell Rep 27 (12):3618–3628 e3615. https://doi.org/10.1016/j.celrep.2019.05.059
de Charette M, Marabelle A, Houot R (2016) Turning tumour cells into antigen presenting cells: the next step to improve cancer immunotherapy? Eur J Cancer 68:134–147. https://doi.org/10.1016/j.ejca.2016.09.010
Article CAS PubMed Google Scholar
Dedhia PH, Bertaux-Skeirik N, Zavros Y, Spence JR (2016) Organoid models of human gastrointestinal development and disease. Gastroenterology 150(5):1098–1112. https://doi.org/10.1053/j.gastro.2015.12.042
Article PubMed Google Scholar
DeWard AD, Cramer J, Lagasse E (2014) Cellular heterogeneity in the mouse esophagus implicates the presence of a nonquiescent epithelial stem cell population. Cell Rep 9(2):701–711. https://doi.org/10.1016/j.celrep.2014.09.027
Article CAS PubMed PubMed Central Google Scholar
Dijkstra KK, Cattaneo CM, Weeber F, Chalabi M, van de Haar J, Fanchi LF, Slagter M, van der Velden DL, Kaing S, Kelderman S, van Rooij N, van Leerdam ME, Depla A, Smit EF, Hartemink KJ, de Groot R, Wolkers MC, Sachs N, Snaebjornsson P, Monkhorst K, Haanen J, Clevers H, Schumacher TN, Voest EE (2018) Generation of tumor-reactive T cells by co-culture of peripheral blood lymphocytes and tumor organoids. Cell 174(6):1586–1598.e1512. https://doi.org/10.1016/j.cell.2018.07.009
Article CAS PubMed PubMed Central Google Scholar
Ding L, Hayes MM, Photenhauer A, Eaton KA, Li Q, Ocadiz-Ruiz R, Merchant JL (2016) Schlafen 4-expressing myeloid-derived suppressor cells are induced during murine gastric metaplasia. J Clin Invest 126(8):2867–2880. https://doi.org/10.1172/jci82529
Article PubMed PubMed Central Google Scholar
Ding L, Li Q, Chakrabarti J, Munoz A, Faure-Kumar E, Ocadiz-Ruiz R, Razumilava N, Zhang G, Hayes MH, Sontz RA, Mendoza ZE, Mahurkar S, Greenson JK, Perez-Perez G, Hanh NTH, Zavros Y, Samuelson LC, Iliopoulos D, Merchant JL (2020) MiR130b from Schlafen4(+) MDSCs stimulates epithelial proliferation and correlates with preneoplastic changes prior to gastric cancer. Gut. https://doi.org/10.1136/gutjnl-2019-318817
Article PubMed Google Scholar
Dye BR, Hill DR, Ferguson MA, Tsai YH, Nagy MS, Dyal R, Wells JM, Mayhew CN, Nattiv R, Klein OD, White ES, Deutsch GH, Spence JR (2015) In vitro generation of human pluripotent stem cell derived lung organoids. Elife 4. https://doi.org/10.7554/elife.05098
Engevik AC, Feng R, Choi E, White S, Bertaux-Skeirik N, Li J, Mahe MM, Aihara E, Yang L, DiPasquale B, Oh S, Engevik KA, Giraud AS, Montrose MH, Medvedovic M, Helmrath MA, Goldenring JR, Zavros Y (2016) The development of spasmolytic polypeptide/TFF2-expressing metaplasia (SPEM) during gastric repair is absent in the aged stomach. Cell Mol Gastroenterol Hepatol 2(5):605–624. https://doi.org/10.1016/j.jcmgh.2016.05.004
Article PubMed PubMed Central Google Scholar
Ettayebi K, Crawford SE, Murakami K, Broughman JR, Karandikar U, Tenge VR, Neill FH, Blutt SE, Zeng XL, Qu L, Kou B, Opekun AR, Burrin D, Graham DY, Ramani S, Atmar RL, Estes MK (2016) Replication of human noroviruses in stem cell-derived human enteroids. Science 353(6306):1387–1393. https://doi.org/10.1126/science.aaf5211
Article PubMed PubMed Central Google Scholar
Farin HF, Karthaus WR, Kujala P, Rakhshandehroo M, Schwank G, Vries RG, Kalkhoven E, Nieuwenhuis EE, Clevers H (2014) Paneth cell extrusion and release of antimicrobial products is directly controlled by immune cell-derived IFN-γ. J Exp Med 211(7):1393–1405. https://doi.org/10.1084/jem.20130753
Article CAS PubMed PubMed Central Google Scholar
Finkbeiner SR, Hill DR, Altheim CH, Dedhia PH, Taylor MJ, Tsai YH, Chin AM, Mahe MM, Watson CL, Freeman JJ, Nattiv R, Thomson M, Klein OD, Shroyer NF, Helmrath MA, Teitelbaum DH, Dempsey PJ, Spence JR (2015) Transcriptome-wide analysis reveals hallmarks of human intestine development and maturation in vitro and in vivo. Stem Cell Rep 4(6):1140–1155. https://doi.org/10.1016/j.stemcr.2015.04.010
Article CAS Google Scholar
Forbester JL, Goulding D, Vallier L, Hannan N, Hale C, Pickard D, Mukhopadhyay S, Dougan G (2015) Interaction of Salmonella enterica serovar typhimurium with intestinal organoids derived from human induced pluripotent stem cells. Infect Immun 83(7):2926–2934. https://doi.org/10.1128/iai.00161-15
Article CAS PubMed PubMed Central Google Scholar
Forster R, Chiba K, Schaeffer L, Regalado SG, Lai CS, Gao Q, Kiani S, Farin HF, Clevers H, Cost GJ, Chan A, Rebar EJ, Urnov FD, Gregory PD, Pachter L, Jaenisch R, Hockemeyer D (2014) Human intestinal tissue with adult stem cell properties derived from pluripotent stem cells. Stem Cell Rep 2(6):838–852. https://doi.org/10.1016/j.stemcr.2014.05.001
Article CAS Google Scholar
Garcez PP, Loiola EC, Madeiro da Costa R, Higa LM, Trindade P, Delvecchio R, Nascimento JM, Brindeiro R, Tanuri A, Rehen SK (2016) Zika virus impairs growth in human neurospheres and brain organoids. Science 352(6287):816–818. https://doi.org/10.1126/science.aaf6116
Article CAS PubMed Google Scholar
Gopalakrishnan V, Spencer CN, Nezi L, Reuben A, Andrews MC, Karpinets TV, Prieto PA, Vicente D, Hoffman K, Wei SC, Cogdill AP, Zhao L, Hudgens CW, Hutchinson DS, Manzo T, Petaccia de Macedo M, Cotechini T, Kumar T, Chen WS, Reddy SM, Szczepaniak Sloane R, Galloway-Pena J, Jiang H, Chen PL, Shpall EJ, Rezvani K, Alousi AM, Chemaly RF, Shelburne S, Vence LM, Okhuysen PC, Jensen VB, Swennes AG, McAllister F, Marcelo Riquelme Sanchez E, Zhang Y, Le Chatelier E, Zitvogel L, Pons N, Austin-Breneman JL, Haydu LE, Burton EM, Gardner JM, Sirmans E, Hu J, Lazar AJ, Tsujikawa T, Diab A, Tawbi H, Glitza IC, Hwu WJ, Patel SP, Woodman SE, Amaria RN, Davies MA, Gershenwald JE, Hwu P, Lee JE, Zhang J, Coussens LM, Cooper ZA, Futreal PA, Daniel CR, Ajami NJ, Petrosino JF, Tetzlaff MT, Sharma P, Allison JP, Jenq RR, Wargo JA (2018) Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients. Science 359(6371):97–103. https://doi.org/10.1126/science.aan4236
Article CAS PubMed Google Scholar
Greggio C, De Franceschi F, Figueiredo-Larsen M, Gobaa S, Ranga A, Semb H, Lutolf M, Grapin-Botton A (2013) Artificial three-dimensional niches deconstruct pancreas development in vitro. Development 140(21):4452–4462. https://doi.org/10.1242/dev.096628
Article CAS PubMed PubMed Central Google Scholar
Guillerme JB, Boisgerault N, Roulois D, Ménager J, Combredet C, Tangy F, Fonteneau JF, Gregoire M (2013) Measles virus vaccine-infected tumor cells induce tumor antigen cross-presentation by human plasmacytoid dendritic cells. Clin Cancer Res 19(5):1147–1158. https://doi.org/10.1158/1078-0432.Ccr-12-2733
Article CAS PubMed Google Scholar
Hannan NR, Fordham RP, Syed YA, Moignard V, Berry A, Bautista R, Hanley NA, Jensen KB, Vallier L (2013) Generation of multipotent foregut stem cells from human pluripotent stem cells. Stem Cell Rep 1(4):293–306. https://doi.org/10.1016/j.stemcr.2013.09.003
Article CAS Google Scholar
Hockemeyer D, Jaenisch R (2016) Induced pluripotent stem cells meet genome editing. Cell Stem Cell 18(5):573–586. https://doi.org/10.1016/j.stem.2016.04.013
Article CAS PubMed PubMed Central Google Scholar
Holokai L, Chakrabarti J, Broda T, Chang J, Hawkins JA, Sundaram N, Wroblewski LE, Peek RM Jr, Wang J, Helmrath M, Wells JM, Zavros Y (2019) Increased programmed death-ligand 1 is an early epithelial cell response to helicobacter pylori infection. PLoS Pathog 15(1):e1007468. https://doi.org/10.1371/journal.ppat.1007468
Article CAS PubMed PubMed Central Google Scholar
Hrvatin S, O’Donnell CW, Deng F, Millman JR, Pagliuca FW, DiIorio P, Rezania A, Gifford DK, Melton DA (2014) Differentiated human stem cells resemble fetal, not adult, β cells. Proc Natl Acad Sci U S A 111(8):3038–3043. https://doi.org/10.1073/pnas.1400709111
Article CAS PubMed PubMed Central Google Scholar
Huch M, Dorrell C, Boj SF, van Es JH, Li VS, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries RG, Grompe M, Clevers H (2013) In vitro expansion of single Lgr5 + liver stem cells induced by Wnt-driven regeneration. Nature 494(7436):247–250. https://doi.org/10.1038/nature11826
Article CAS PubMed PubMed Central Google Scholar
Huch M, Koo BK (2015) Modeling mouse and human development using organoid cultures. Development 142(18):3113–3125. https://doi.org/10.1242/dev.118570
Article CAS PubMed Google Scholar
Jung P, Sato T, Merlos-Suárez A, Barriga FM, Iglesias M, Rossell D, Auer H, Gallardo M, Blasco MA, Sancho E, Clevers H, Batlle E (2011) Isolation and in vitro expansion of human colonic stem cells. Nat Med 17(10):1225–1227. https://doi.org/10.1038/nm.2470
Article CAS PubMed Google Scholar
Kalabis J, Wong GS, Vega ME, Natsuizaka M, Robertson ES, Herlyn M, Nakagawa H, Rustgi AK (2012) Isolation and characterization of mouse and human esophageal epithelial cells in 3D organotypic culture. Nat Protoc 7(2):235–246. https://doi.org/10.1038/nprot.2011.437
Article CAS PubMed PubMed Central Google Scholar
Leslie JL, Huang S, Opp JS, Nagy MS, Kobayashi M, Young VB, Spence JR (2015) Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect Immun 83(1):138–145. https://doi.org/10.1128/iai.02561-14
Article PubMed Google Scholar
Marshall BJ, Warren JR (1984) Unidentified curved bacilli in the stomach of patients with gastritis and peptic ulceration. Lancet 1(8390):1311–1315. https://doi.org/10.1016/s0140-6736(84)91816-6
Article CAS PubMed Google Scholar
Matson V, Fessler J, Bao R, Chongsuwat T, Zha Y, Alegre ML, Luke JJ, Gajewski TF (2018) The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients. Science 359(6371):104–108. https://doi.org/10.1126/science.aao3290
Article CAS PubMed PubMed Central Google Scholar
Matsueda S, Graham DY (2014) Immunotherapy in gastric cancer. World J Gastroenterol 20(7):1657–1666. https://doi.org/10.3748/wjg.v20.i7.1657
Article CAS PubMed PubMed Central Google Scholar
McCauley HA, Wells JM (2017) Pluripotent stem cell-derived organoids: using principles of developmental biology to grow human tissues in a dish. Development 144(6):958–962. https://doi.org/10.1242/dev.140731
Article CAS PubMed PubMed Central Google Scholar
McCracken KW, Aihara E, Martin B, Crawford CM, Broda T, Treguier J, Zhang X, Shannon JM, Montrose MH, Wells JM (2017) Wnt/β-catenin promotes gastric fundus specification in mice and humans. Nature 541(7636):182–187. https://doi.org/10.1038/nature21021
Article CAS PubMed PubMed Central Google Scholar
McCracken KW, Catá EM, Crawford CM, Sinagoga KL, Schumacher M, Rockich BE, Tsai YH, Mayhew CN, Spence JR, Zavros Y, Wells JM (2014) Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516(7531):400–404. https://doi.org/10.1038/nature13863
Article CAS PubMed PubMed Central Google Scholar
McCracken KW, Howell JC, Wells JM, Spence JR (2011) Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc 6(12):1920–1928. https://doi.org/10.1038/nprot.2011.410
Article CAS PubMed PubMed Central Google Scholar
Michels BE, Mosa MH, Grebbin BM, Yepes D, Darvishi T, Hausmann J, Urlaub H, Zeuzem S, Kvasnicka HM, Oellerich T, Farin HF (2019) Human colon organoids reveal distinct physiologic and oncogenic Wnt responses. J Exp Med 216(3):704–720. https://doi.org/10.1084/jem.20180823
Article CAS PubMed PubMed Central Google Scholar
Millán O, Rafael-Valdivia L, Torrademé E, López A, Fortuna V, Sánchez-Cabus S, López-Púa Y, Rimola A, Brunet M (2013) Intracellular IFN-γ and IL-2 expression monitoring as surrogate markers of the risk of acute rejection and personal drug response in de novo liver transplant recipients. Cytokine 61(2):556–564. https://doi.org/10.1016/j.cyto.2012.10.026
Article CAS PubMed Google Scholar
Neal JT, Li X, Zhu J, Giangarra V, Grzeskowiak CL, Ju J, Liu IH, Chiou SH, Salahudeen AA, Smith AR, Deutsch BC, Liao L, Zemek AJ, Zhao F, Karlsson K, Schultz LM, Metzner TJ, Nadauld LD, Tseng YY, Alkhairy S, Oh C, Keskula P, Mendoza-Villanueva D, De La Vega FM, Kunz PL, Liao JC, Leppert JT, Sunwoo JB, Sabatti C, Boehm JS, Hahn WC, Zheng GXY, Davis MM, Kuo CJ (2018) Organoid modeling of the tumor immune microenvironment. Cell 175(7):1972–1988.e1916. https://doi.org/10.1016/j.cell.2018.11.021
Article CAS PubMed PubMed Central Google Scholar
Noel G, Baetz NW, Staab JF, Donowitz M, Kovbasnjuk O, Pasetti MF, Zachos NC (2017) A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions. Sci Rep 7:45270. https://doi.org/10.1038/srep45270
Article CAS PubMed PubMed Central Google Scholar
Nozaki K, Mochizuki W, Matsumoto Y, Matsumoto T, Fukuda M, Mizutani T, Watanabe M, Nakamura T (2016) Co-culture with intestinal epithelial organoids allows efficient expansion and motility analysis of intraepithelial lymphocytes. J Gastroenterol 51(3):206–213. https://doi.org/10.1007/s00535-016-1170-8
Article CAS PubMed PubMed Central Google Scholar
Odenbreit S, Püls J, Sedlmaier B, Gerland E, Fischer W, Haas R (2000) Translocation of helicobacter pylori CagA into gastric epithelial cells by type IV secretion. Science 287(5457):1497–1500. https://doi.org/10.1126/science.287.5457.1497
Article CAS PubMed Google Scholar
Ootani A, Li X, Sangiorgi E, Ho QT, Ueno H, Toda S, Sugihara H, Fujimoto K, Weissman IL, Capecchi MR, Kuo CJ (2009) Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med 15(6):701–706. https://doi.org/10.1038/nm.1951
Article CAS PubMed PubMed Central Google Scholar
Qian X, Nguyen HN, Jacob F, Song H, Ming GL (2017) Using brain organoids to understand Zika virus-induced microcephaly. Development 144(6):952–957. https://doi.org/10.1242/dev.140707
Article CAS PubMed PubMed Central Google Scholar
Randall KJ, Turton J, Foster JR (2011) Explant culture of gastrointestinal tissue: a review of methods and applications. Cell Biol Toxicol 27(4):267–284. https://doi.org/10.1007/s10565-011-9187-5
Article PubMed Google Scholar
Rogoz A, Reis BS, Karssemeijer RA, Mucida D (2015) A 3-D enteroid-based model to study T-cell and epithelial cell interaction. J Immunol Methods 421:89–95. https://doi.org/10.1016/j.jim.2015.03.014
Article CAS PubMed PubMed Central Google Scholar
Routy B, Gopalakrishnan V, Daillère R, Zitvogel L, Wargo JA, Kroemer G (2018) The gut microbiota influences anticancer immunosurveillance and general health. Nat Rev Clin Oncol 15(6):382–396. https://doi.org/10.1038/s41571-018-0006-2
Article CAS PubMed Google Scholar
Sato S, Hisaie K, Kurokawa S, Suzuki A, Sakon N, Uchida Y, Yuki Y, Kiyono H (2019) Human norovirus propagation in human induced pluripotent stem cell-derived intestinal epithelial cells. Cell Mol Gastroenterol Hepatol 7(3):686–688.e685. https://doi.org/10.1016/j.jcmgh.2018.11.001
Article PubMed Google Scholar
Sato T, Stange DE, Ferrante M, Vries RG, Van Es JH, Van den Brink S, Van Houdt WJ, Pronk A, Van Gorp J, Siersema PD, Clevers H (2011a) Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141(5):1762–1772. https://doi.org/10.1053/j.gastro.2011.07.050
Article CAS PubMed Google Scholar
Sato T, van Es JH, Snippert HJ, Stange DE, Vries RG, van den Born M, Barker N, Shroyer NF, van de Wetering M, Clevers H (2011b) Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature 469(7330):415–418. https://doi.org/10.1038/nature09637
Article CAS PubMed Google Scholar
Sato T, Vries RG, Snippert HJ, van de Wetering M, Barker N, Stange DE, van Es JH, Abo A, Kujala P, Peters PJ, Clevers H (2009) Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature 459(7244):262–265. https://doi.org/10.1038/nature07935
Article CAS PubMed Google Scholar
Saxena K, Blutt SE, Ettayebi K, Zeng XL, Broughman JR, Crawford SE, Karandikar UC, Sastri NP, Conner ME, Opekun AR, Graham DY, Qureshi W, Sherman V, Foulke-Abel J, In J, Kovbasnjuk O, Zachos NC, Donowitz M, Estes MK (2016) Human intestinal enteroids: a new model to study human rotavirus infection, host restriction, and pathophysiology. J Virol 90(1):43–56. https://doi.org/10.1128/jvi.01930-15
Article CAS PubMed Google Scholar
Schmeichel KL, Bissell MJ (2003) Modeling tissue-specific signaling and organ function in three dimensions. J Cell Sci 116(Pt 12):2377–2388. https://doi.org/10.1242/jcs.00503
Article CAS PubMed Google Scholar
Schouppe E, Van Overmeire E, Laoui D, Keirsse J, Van Ginderachter JA (2013) Modulation of CD8(+) T-cell activation events by monocytic and granulocytic myeloid-derived suppressor cells. Immunobiology 218(11):1385–1391. https://doi.org/10.1016/j.imbio.2013.07.003
Article CAS PubMed Google Scholar
Schumacher MA, Aihara E, Feng R, Engevik A, Shroyer NF, Ottemann KM, Worrell RT, Montrose MH, Shivdasani RA, Zavros Y (2015) The use of murine-derived fundic organoids in studies of gastric physiology. J Physiol 593(8):1809–1827. https://doi.org/10.1113/jphysiol.2014.283028
Article CAS PubMed PubMed Central Google Scholar
Schumacher MA, Donnelly JM, Engevik AC, Xiao C, Yang L, Kenny S, Varro A, Hollande F, Samuelson LC, Zavros Y (2012) Gastric Sonic Hedgehog acts as a macrophage chemoattractant during the immune response to Helicobacter pylori. Gastroenterology 142(5):1150–1159.e1156. https://doi.org/10.1053/j.gastro.2012.01.029
Article CAS PubMed Google Scholar
Sehgal K, Dhodapkar KM, Dhodapkar MV (2014) Targeting human dendritic cells in situ to improve vaccines. Immunol Lett 162 (1 Pt A):59–67. https://doi.org/10.1016/j.imlet.2014.07.004
Shan J, Schwartz RE, Ross NT, Logan DJ, Thomas D, Duncan SA, North TE, Goessling W, Carpenter AE, Bhatia SN (2013) Identification of small molecules for human hepatocyte expansion and iPS differentiation. Nat Chem Biol 9(8):514–520. https://doi.org/10.1038/nchembio.1270
Article CAS PubMed PubMed Central Google Scholar
Si-Tayeb K, Noto FK, Nagaoka M, Li J, Battle MA, Duris C, North PE, Dalton S, Duncan SA (2010) Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cells. Hepatology 51(1):297–305. https://doi.org/10.1002/hep.23354
Article CAS PubMed Google Scholar
Sivan A, Corrales L, Hubert N, Williams JB, Aquino-Michaels K, Earley ZM, Benyamin FW, Lei YM, Jabri B, Alegre ML, Chang EB, Gajewski TF (2015) Commensal Bifidobacterium promotes antitumor immunity and facilitates anti-PD-L1 efficacy. Science 350(6264):1084–1089. https://doi.org/10.1126/science.aac4255
Article CAS PubMed PubMed Central Google Scholar
Spence JR, Mayhew CN, Rankin SA, Kuhar MF, Vallance JE, Tolle K, Hoskins EE, Kalinichenko VV, Wells SI, Zorn AM, Shroyer NF, Wells JM (2011) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470(7332):105–109. https://doi.org/10.1038/nature09691
Article CAS PubMed Google Scholar
Stange DE, Koo BK, Huch M, Sibbel G, Basak O, Lyubimova A, Kujala P, Bartfeld S, Koster J, Geahlen JH, Peters PJ, van Es JH, van de Wetering M, Mills JC, Clevers H (2013) Differentiated Troy + chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155(2):357–368. https://doi.org/10.1016/j.cell.2013.09.008
Article CAS PubMed PubMed Central Google Scholar
Steele NG, Chakrabarti J, Wang J, Biesiada J, Holokai L, Chang J, Nowacki LM, Hawkins J, Mahe M, Sundaram N, Shroyer N, Medvedovic M, Helmrath M, Ahmad S, Zavros Y (2019) An organoid-based preclinical model of human gastric cancer. Cell Mol Gastroenterol Hepatol 7(1):161–184. https://doi.org/10.1016/j.jcmgh.2018.09.008
Article PubMed Google Scholar
Strangeways TS, Canti RG (1926) Dark-ground illumination of tissue cells cultivated “in vitro”. Br Med J 2 (3420):155–157. https://doi.org/10.1136/bmj.2.3420.155
Takahashi K, Tanabe K, Ohnuki M, Narita M, Ichisaka T, Tomoda K, Yamanaka S (2007) Induction of pluripotent stem cells from adult human fibroblasts by defined factors. Cell 131(5):861–872. https://doi.org/10.1016/j.cell.2007.11.019
Article CAS PubMed Google Scholar
Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, Zhang RR, Ueno Y, Zheng YW, Koike N, Aoyama S, Adachi Y, Taniguchi H (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499(7459):481–484. https://doi.org/10.1038/nature12271
Article CAS PubMed Google Scholar
Thara E, Dorff TB, Pinski JK, Quinn DI (2011) Vaccine therapy with sipuleucel-T (Provenge) for prostate cancer. Maturitas 69(4):296–303. https://doi.org/10.1016/j.maturitas.2011.04.012
Article CAS PubMed Google Scholar
Thomson JA, Itskovitz-Eldor J, Shapiro SS, Waknitz MA, Swiergiel JJ, Marshall VS, Jones JM (1998) Embryonic stem cell lines derived from human blastocysts. Science 282(5391):1145–1147. https://doi.org/10.1126/science.282.5391.1145
Article CAS PubMed Google Scholar
Tiriac H, Belleau P, Engle DD, Plenker D, Deschênes A, Somerville TDD, Froeling FEM, Burkhart RA, Denroche RE, Jang GH, Miyabayashi K, Young CM, Patel H, Ma M, LaComb JF, Palmaira RLD, Javed AA, Huynh JC, Johnson M, Arora K, Robine N, Shah M, Sanghvi R, Goetz AB, Lowder CY, Martello L, Driehuis E, LeComte N, Askan G, Iacobuzio-Donahue CA, Clevers H, Wood LD, Hruban RH, Thompson E, Aguirre AJ, Wolpin BM, Sasson A, Kim J, Wu M, Bucobo JC, Allen P, Sejpal DV, Nealon W, Sullivan JD, Winter JM, Gimotty PA, Grem JL, DiMaio DJ, Buscaglia JM, Grandgenett PM, Brody JR, Hollingsworth MA, O’Kane GM, Notta F, Kim E, Crawford JM, Devoe C, Ocean A, Wolfgang CL, Yu KH, Li E, Vakoc CR, Hubert B, Fischer SE, Wilson JM, Moffitt R, Knox J, Krasnitz A, Gallinger S, Tuveson DA (2018) Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov 8(9):1112–1129. https://doi.org/10.1158/2159-8290.Cd-18-0349
Article CAS PubMed PubMed Central Google Scholar
Tsai S, McOlash L, Palen K, Johnson B, Duris C, Yang Q, Dwinell MB, Hunt B, Evans DB, Gershan J, James MA (2018) Development of primary human pancreatic cancer organoids, matched stromal and immune cells and 3D tumor microenvironment models. BMC Cancer 18(1):335. https://doi.org/10.1186/s12885-018-4238-4
Article CAS PubMed PubMed Central Google Scholar
van de Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, van Houdt W, van Gorp J, Taylor-Weiner A, Kester L, McLaren-Douglas A, Blokker J, Jaksani S, Bartfeld S, Volckman R, van Sluis P, Li VS, Seepo S, Sekhar Pedamallu C, Cibulskis K, Carter SL, McKenna A, Lawrence MS, Lichtenstein L, Stewart C, Koster J, Versteeg R, van Oudenaarden A, Saez-Rodriguez J, Vries RG, Getz G, Wessels L, Stratton MR, McDermott U, Meyerson M, Garnett MJ, Clevers H (2015) Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161(4):933–945. https://doi.org/10.1016/j.cell.2015.03.053
Article CAS PubMed PubMed Central Google Scholar
Wang L, Chang EW, Wong SC, Ong SM, Chong DQ, Ling KL (2013) Increased myeloid-derived suppressor cells in gastric cancer correlate with cancer stage and plasma S100A8/A9 proinflammatory proteins. J Immunol 190(2):794–804. https://doi.org/10.4049/jimmunol.1202088
Article CAS PubMed Google Scholar
Watson CL, Mahe MM, Múnera J, Howell JC, Sundaram N, Poling HM, Schweitzer JI, Vallance JE, Mayhew CN, Sun Y, Grabowski G, Finkbeiner SR, Spence JR, Shroyer NF, Wells JM, Helmrath MA (2014) An in vivo model of human small intestine using pluripotent stem cells. Nat Med 20(11):1310–1314. https://doi.org/10.1038/nm.3737
Article CAS PubMed PubMed Central Google Scholar
Xu H, Jiao Y, Qin S, Zhao W, Chu Q, Wu K (2018) Organoid technology in disease modelling, drug development, personalized treatment and regeneration medicine. Exp Hematol Oncol 7:30. https://doi.org/10.1186/s40164-018-0122-9
Article CAS PubMed PubMed Central Google Scholar
Youn JI, Nagaraj S, Collazo M, Gabrilovich DI (2008) Subsets of myeloid-derived suppressor cells in tumor-bearing mice. J Immunol 181(8):5791–5802. https://doi.org/10.4049/jimmunol.181.8.5791
Article CAS PubMed Google Scholar
Zhang Y, Velez-Delgado A, Mathew E, Li D, Mendez FM, Flannagan K, Rhim AD, Simeone DM, Beatty GL, Pasca di Magliano M (2017) Myeloid cells are required for PD-1/PD-L1 checkpoint activation and the establishment of an immunosuppressive environment in pancreatic cancer. Gut 66(1):124–136. https://doi.org/10.1136/gutjnl-2016-312078
Article CAS PubMed Google Scholar
Zhang ZH, Yu LJ, Hui XC, Wu ZZ, Yin KL, Yang H, Xu Y (2014) Hydroxy-safflor yellow A attenuates Aβ_1–42-induced inflammation by modulating the JAK2/STAT3/NF-κB pathway. Brain Res 1563:72–80. https://doi.org/10.1016/j.brainres.2014.03.036
Article CAS PubMed Google Scholar
Zhao L, Niu C, Shi X, Xu D, Li M, Cui J, Li W, Xu J, Jin H (2018) Dendritic cells loaded with the lysate of tumor cells infected with Newcastle Disease Virus trigger potent anti-tumor immunity by promoting the secretion of IFN-γ and IL-2 from T cells. Oncol Lett 16(1):1180–1188. https://doi.org/10.3892/ol.2018.8785
Article CAS PubMed PubMed Central Google Scholar
Zumwalde NA, Haag JD, Sharma D, Mirrielees JA, Wilke LG, Gould MN, Gumperz JE (2016) Analysis of immune cells from human mammary ductal epithelial organoids reveals Vδ2 + T cells that efficiently target breast carcinoma cells in the presence of bisphosphonate. Cancer Prev Res (Phila) 9(4):305–316. https://doi.org/10.1158/1940-6207.Capr-15-0370-t
Article CAS Google Scholar

Download references

Acknowledgements

We are sincerely grateful for the collaboration and support by Dr. James Wells (Division of Developmental Biology, Center for Stem Cell & Organoid Medicine, Division of Endocrinology, Cincinnati Children’s Hospital Medical Center) and Dr. Michael Helmrath (Department of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center). This work was supported by NIH (NIAID) 5U19AI11649105 (PIs: Weiss and Wells, Project Leader 1: Zavros) and NIH R01DK083402-10 (PI: Zavros).

Author information

Authors and Affiliations

Department of Cellular and Molecular Medicine, University of Arizona College of Medicine-Tucson, 1333 N. Martin Avenue, LSN 412, Tucson, AZ 85719-0000, AZ, USA
Jayati Chakrabarti & Yana Zavros
Department of Pharmacology and Systems Physiology, University of Cincinnati College of Medicine, 231 Albert Sabin Way, MSB 4202, Cincinnati, OH 45267-0000, OH, USA
Martha B. Dua-Awereh
Merck Pharmaceuticals, San Francisco, CA, USA
Loryn Holokai

Authors

Jayati Chakrabarti
View author publications
You can also search for this author in PubMed Google Scholar
Martha B. Dua-Awereh
View author publications
You can also search for this author in PubMed Google Scholar
Loryn Holokai
View author publications
You can also search for this author in PubMed Google Scholar
Yana Zavros
View author publications
You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yana Zavros .

Editor information

Editors and Affiliations

GSK Vaccines Research, Siena, Italy
Fabio Bagnoli
GSK Vaccines Research, Siena, Italy
Rino Rappuoli

Rights and permissions

Reprints and permissions

Copyright information

About this chapter

Cite this chapter

Chakrabarti, J., Dua-Awereh, M.B., Holokai, L., Zavros, Y. (2021). Human Gastrointestinal Organoid Models for Studying Microbial Disease and Cancer. In: Bagnoli, F., Rappuoli, R. (eds) Three Dimensional Human Organotypic Models for Biomedical Research. Current Topics in Microbiology and Immunology, vol 430. Springer, Cham. https://doi.org/10.1007/82_2020_223

Download citation

DOI: https://doi.org/10.1007/82_2020_223
Published: 06 September 2020
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-62451-4
Online ISBN: 978-3-030-62452-1
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)

Publish with us

Policies and ethics