Skip to main content

Advertisement

SpringerLink
Log in

Esophageal organoids: applications and future prospects

  • Review
  • Published:
Journal of Molecular Medicine Aims and scope Submit manuscript

Abstract

Organoids have been developed in the last decade as a new research tool to simulate organ cell biology and disease. Compared to traditional 2D cell lines and animal models, experimental data based on esophageal organoids are more reliable. In recent years, esophageal organoids derived from multiple cell sources have been established, and relatively mature culture protocols have been developed. Esophageal inflammation and cancer are two directions of esophageal organoid modeling, and organoid models of esophageal adenocarcinoma, esophageal squamous cell carcinoma, and eosinophilic esophagitis have been established. The properties of esophageal organoids, which mimic the real esophagus, contribute to research in drug screening and regenerative medicine. The combination of organoids with other technologies, such as organ chips and xenografts, can complement the deficiencies of organoids and create entirely new research models that are more advantageous for cancer research. In this review, we will summarize the development of tumor and non-tumor esophageal organoids, the current application of esophageal organoids in disease modeling, regenerative medicine, and drug screening. We will also discuss the future prospects of esophageal organoids.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

References

  1. Uhlenhopp DJ, Then EO, Sunkara T et al (2020) Epidemiology of esophageal cancer: update in global trends, etiology and risk factors. Clin J Gastroenterol 13(6):1010–1021. https://doi.org/10.1007/s12328-020-01237-x

    Article  PubMed  Google Scholar 

  2. Peters Y, Al-Kaabi A, Shaheen NJ et al (2019) Barrett oesophagus Nat Rev Dis Primers 5(1):35. https://doi.org/10.1038/s41572-019-0086-z

    Article  PubMed  Google Scholar 

  3. GBD (2017) Oesophageal Cancer Collaborators (2020) The global, regional, and national burden of oesophageal cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 5(6):582–597. https://doi.org/10.1016/S2468-1253(20)30007-8

    Article  Google Scholar 

  4. Sawas T, Killcoyne S, Iyer PG et al (2018) Identification of prognostic phenotypes of esophageal adenocarcinoma in 2 independent cohorts. Gastroenterology 155(6):1720–1728.e4. https://doi.org/10.1053/j.gastro.2018.08.036

    Article  PubMed  Google Scholar 

  5. Molina-Infante J, Schoepfer AM, Lucendo AJ et al (2017) Eosinophilic esophagitis: what can we learn from Crohn’s disease? United European Gastroenterol J 5(6):762–772. https://doi.org/10.1177/2050640616672953

    Article  PubMed  Google Scholar 

  6. Ng SC, Shi HY, Hamidi N et al (2017) Worldwide incidence and prevalence of inflammatory bowel disease in the 21st century: a systematic review of population-based studies. Lancet 390(10114):2769–2778. https://doi.org/10.1016/S0140-6736(17)32448-0

    Article  PubMed  Google Scholar 

  7. Ishimura N, Okimoto E, Shibagaki K et al (2021) Similarity and difference in the characteristics of eosinophilic esophagitis between Western countries and Japan. Dig Endosc 33(5):708–719

  8. Rossi G, Manfrin A, Lutolf MP (2018) Progress and potential in organoid research. Nat Rev Genet 19(11):671–687. https://doi.org/10.1038/s41576-018-0051-9

    Article  CAS  PubMed  Google Scholar 

  9. Sato T, Vries RG, Snippert HJ et al (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 

  10. Nguyen R, Da Won BS, Qiao L et al (2021) Developing liver organoids from induced pluripotent stem cells (iPSCs): an alternative source of organoid generation for liver cancer research. Cancer Lett 508:13–17. https://doi.org/10.1016/j.canlet.2021.03.017

    Article  CAS  PubMed  Google Scholar 

  11. Zhu X, Zhang B, He Y et al (2021) Liver organoids: formation strategies and biomedical applications. Tissue Eng Regen Med 18(4):573–585. https://doi.org/10.1007/s13770-021-00357-w

    Article  PubMed  PubMed Central  Google Scholar 

  12. Hohwieler M, Illing A, Hermann PC et al (2017) Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut 66(3):473–486. https://doi.org/10.1136/gutjnl-2016-312423

    Article  CAS  PubMed  Google Scholar 

  13. Grenier K, Kao J, Diamandis P (2020) Three-dimensional modeling of human neurodegeneration: brain organoids coming of age. Mol Psychiatry 25(2):254–274. https://doi.org/10.1038/s41380-019-0500-7

    Article  PubMed  Google Scholar 

  14. Seidlitz T, Merker SR, Rothe A et al (2019) Human gastric cancer modelling using organoids. Gut 68(2):207–217. https://doi.org/10.1136/gutjnl-2017-314549

    Article  CAS  PubMed  Google Scholar 

  15. Quante M, Bhagat G, Abrams JA et al (2012) Bile acid and inflammation activate gastric cardia stem cells in a mouse model of Barrett-like metaplasia. Cancer Cell 21(1):36–51. https://doi.org/10.1016/j.ccr.2011.12.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tang XH, Knudsen B, Bemis D et al (2004) Oral cavity and esophageal carcinogenesis modeled in carcinogen-treated mice. Clin Cancer Res 10(1 Pt 1):301–313. https://doi.org/10.1158/1078-0432.ccr-0999-3

    Article  CAS  PubMed  Google Scholar 

  17. Stairs DB, Bayne LJ, Rhoades B et al (2011) Deletion of p120-catenin results in a tumor microenvironment with inflammation and cancer that establishes it as a tumor suppressor gene. Cancer Cell 19(4):470–483. https://doi.org/10.1016/j.ccr.2011.02.007

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Opitz OG, Harada H, Suliman Y et al (2002) A mouse model of human oral-esophageal cancer. J Clin Invest 110(6):761–769. https://doi.org/10.1172/JCI15324

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Camilleri AE, Nag S, Russo AR et al (2021) Gene therapy for a murine model of eosinophilic esophagitis. Allergy 76(9):2740–2752. https://doi.org/10.1111/all.14822

    Article  CAS  PubMed  Google Scholar 

  20. Kawaura Y, Tatsuzawa Y, Wakabayashi T et al (2001) Immunohistochemical study of p53, c-erbB-2, and PCNA in Barrett’s esophagus with dysplasia and adenocarcinoma arising from experimental acid or alkaline reflux model. J Gastroenterol 36(9):595–600. https://doi.org/10.1007/s005350170042

    Article  CAS  PubMed  Google Scholar 

  21. Kadirkamanathan SS, Yazaki E, Evans DF et al (2001) An ambulant porcine model of acid reflux used to evaluate endoscopic gastroplasty. Gut 44(6):782–788. https://doi.org/10.1136/gut.44.6.782

    Article  Google Scholar 

  22. Kapoor H, Lohani KR, Lee TH et al (2015) Animal models of Barrett’s esophagus and esophageal adenocarcinoma-past, present, and future. Clin Transl Sci 8(6):841–847. https://doi.org/10.1111/cts.12304

    Article  PubMed  PubMed Central  Google Scholar 

  23. Kruger L, Gonzalez LM, Pridgen TA et al (2017) Ductular and proliferative response of esophageal submucosal glands in a porcine model of esophageal injury and repair. Am J Physiol Gastrointest Liver Physiol 313(3):G180–G191. https://doi.org/10.1152/ajpgi.00036.2017

    Article  PubMed  PubMed Central  Google Scholar 

  24. Harada H, Nakagawa H, Oyama K et al (2003) Telomerase induces immortalization of human esophageal keratinocytes without p16INK4a inactivation. Mol Cancer Res 1(10):729–738

    CAS  PubMed  Google Scholar 

  25. Harada H, Nakagawa H, Takaoka M et al (2008) Cleavage of MCM2 licensing protein fosters senescence in human keratinocytes. Cell Cycle 7(22):3534–3538. https://doi.org/10.4161/cc.7.22.7043

    Article  CAS  PubMed  Google Scholar 

  26. Ohashi S, Natsuizaka M, Wong GS et al (2010) Epidermal growth factor receptor and mutant p53 expand an esophageal cellular subpopulation capable of epithelial-to-mesenchymal transition through ZEB transcription factors. Cancer Res 70(10):4174–4184. https://doi.org/10.1158/0008-5472.CAN-09-4614

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Ohashi S, Natsuizaka M, Yashiro-Ohtani Y et al (2010) NOTCH1 and NOTCH3 coordinate esophageal squamous differentiation through a CSL-dependent transcriptional network. Gastroenterology 139(6):2113–2123. https://doi.org/10.1053/j.gastro.2010.08.040

    Article  CAS  PubMed  Google Scholar 

  28. Whelan KA, Muir AB, Nakagawa H (2018) Esophageal 3D culture systems as modeling tools in esophageal epithelial pathobiology and personalized medicine. Cell Mol Gastroenterol Hepatol 5(4):461–478. https://doi.org/10.1016/j.jcmgh.2018.01.011

    Article  PubMed  PubMed Central  Google Scholar 

  29. Yoshida GJ (2020) Applications of patient-derived tumor xenograft models and tumor organoids. J Hematol Oncol 13(1):4. https://doi.org/10.1186/s13045-019-0829-z

    Article  PubMed  PubMed Central  Google Scholar 

  30. Lan T, Xue X, Dunmall LC et al (2021) Patient-derived xenograft: a developing tool for screening biomarkers and potential therapeutic targets for human esophageal cancers. Aging 13(8):1227–12293. https://doi.org/10.18632/aging.202934

  31. Dodbiba L, Teichman J, Fleet A et al (2013) Primary esophageal and gastro-esophageal junction cancer xenograft models: clinicopathological features and engraftment. Lab Invest 93(4):397–407. https://doi.org/10.1038/labinvest.2013.8

    Article  PubMed  Google Scholar 

  32. Dodbiba L, Teichman J, Fleet A et al (2015) Appropriateness of using patient-derived xenograft models for pharmacologic evaluation of novel therapies for esophageal/gastro-esophageal junction cancers. PLoS One 10(3):e0121872. https://doi.org/10.1371/journal.pone.0121872

  33. Sanchez-Vega F, Hechtman JF, Castel P et al (2019) EGFR and MET amplifications determine response to HER2 inhibition in ERBB2-amplified esophagogastric cancer. Cancer Discov 9(2):199–209. https://doi.org/10.1158/2159-8290.CD-18-0598

    Article  CAS  PubMed  Google Scholar 

  34. Ebbing EA, van der Zalm AP, Steins A et al (2019) Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma. Proc Natl Acad Sci U S A 116(6):2237–2242. https://doi.org/10.1073/pnas.1820459116

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Clevers H (2016) Modeling development and disease with organoids. Cell 165:1586–1597

    Article  CAS  PubMed  Google Scholar 

  36. Sachdeva UM, Shimonosono M, Flashner S et al (2021) Understanding the cellular origin and progression of esophageal cancer using esophageal organoids. Cancer Lett 509:39–52. https://doi.org/10.1016/j.canlet.2021.03.031

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Zhang Y, Yang Y, Jiang M et al (2018) 3D Modeling of esophageal development using human PSC-derived basal progenitors reveals a critical role for Notch signaling. Cell Stem Cell 23(4):516–529.e5. https://doi.org/10.1016/j.stem.2018.08.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Trisno SL, Philo KED, McCracken KW et al (2018) Esophageal organoids from human pluripotent stem cells delineate Sox2 functions during esophageal specification. Cell Stem Cell 23(4):501–515.e7. https://doi.org/10.1016/j.stem.2018.08.008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Schutgens F, Clevers H (2020) Human organoids: tools for understanding biology and treating diseases. Annu Rev Pathol 15:211–234. https://doi.org/10.1146/annurev-pathmechdis-012419-032611

    Article  CAS  PubMed  Google Scholar 

  40. Brassard JA, Lutolf MP (2019) Engineering stem cell self-organization to build better organoids. Cell Stem Cell 24:860–876. https://doi.org/10.1016/j.stem.2019.05.005

    Article  CAS  PubMed  Google Scholar 

  41. Tang XY, Wu S, Wang D et al (2022) Human organoids in basic research and clinical applications. Signal Transduct Target Ther 7(1):168. https://doi.org/10.1038/s41392-022-01024-9

    Article  PubMed  PubMed Central  Google Scholar 

  42. Jiminez JA, Uwiera TC, Douglas Inglis G et al (2015) Animal models to study acute and chronic intestinal inflammation in mammals. Gut Pathog 7:29. https://doi.org/10.1186/s13099-015-0076-y

    Article  PubMed  PubMed Central  Google Scholar 

  43. Sasai Y (2013) Next-generation regenerative medicine: organogenesis from stem cells in 3D culture. Cell Stem Cell 12(5):520–530. https://doi.org/10.1016/j.stem.2013.04.009

    Article  CAS  PubMed  Google Scholar 

  44. He S, Hu B, Li C et al (2018) PDXliver: a database of liver cancer patient derived xenograft mouse models. BMC Cancer 18(1):550. https://doi.org/10.1186/s12885-018-4459-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. 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 

  46. Kasagi Y, Chandramouleeswaran PM, Whelan KA et al (2018) The esophageal organoid system reveals functional interplay between notch and cytokines in reactive epithelial changes. Cell Mol Gastroenterol Hepatol 5(3):333–352. https://doi.org/10.1016/j.jcmgh.2017.12.013

    Article  PubMed  PubMed Central  Google Scholar 

  47. Bailey DD, Zhang Y, van Soldt BJ et al (2019) Use of hPSC-derived 3D organoids and mouse genetics to define the roles of YAP in the development of the esophagus. Development 146(23):dev178855. https://doi.org/10.1242/dev.178855

  48. Sato T, Stange DE, Ferrante M et al (2011) 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 

  49. Li X, Francies HE, Secrier M et al (2018) Organoid cultures recapitulate esophageal adenocarcinoma heterogeneity providing a model for clonality studies and precision therapeutics. Nat Commun 9(1):2983. https://doi.org/10.1038/s41467-018-05190-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Kijima T, Nakagawa H, Shimonosono M et al (2018) Three-dimensional organoids reveal therapy resistance of esophageal and oropharyngeal squamous cell carcinoma cells. Cell Mol Gastroenterol Hepatol 7(1):73–91. https://doi.org/10.1016/j.jcmgh.2018.09.003

    Article  PubMed  PubMed Central  Google Scholar 

  51. Karakasheva T A, Kijima T, Shimonosono M et al (2020) Generation and characterization of patient-derived head and neck, oral, and esophageal cancer organoids. Curr Protoc Stem Cell Biol 53(1):e109. https://doi.org/10.1002/cpsc.109

  52. Zheng B, Ko KP, Fang X et al (2021) A new murine esophageal organoid culture method and organoid-based model of esophageal squamous cell neoplasia. IScience 24(12):103440. https://doi.org/10.1016/j.isci.2021.103440

  53. Fan N, Raatz L, Chon SH et al (2022) Subculture and Cryopreservation of esophageal adenocarcinoma organoids: pros and cons for single cell digestion. J Vis Exp. https://doi.org/10.3791/63281

    Article  PubMed  Google Scholar 

  54. Giobbe GG, Crowley C, Luni C et al (2019) Extracellular matrix hydrogel derived from decellularized tissues enables endodermal organoid culture. Nat Commun 10(1):5658. https://doi.org/10.1038/s41467-019-13605-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Naranjo JD, Saldin LT, Sobieski E et al (2020) Esophageal extracellular matrix hydrogel mitigates metaplastic change in a dog model of Barrett’s esophagus. Sci Adv 6(27):eaba4526. https://doi.org/10.1126/sciadv.aba4526

  56. Curvello R, Kerr G, Micati DJ et al (2020) Engineered plant-based nanocellulose hydrogel for small intestinal organoid growth. Adv Sci (Weinh) 8(1):2002135. https://doi.org/10.1002/advs.202002135

    Article  CAS  PubMed  Google Scholar 

  57. Sorrentino G, Rezakhani S, Yildiz E et al (2020) Mechano-modulatory synthetic niches for liver organoid derivation. Nat Commun 11(1):3416. https://doi.org/10.1038/s41467-020-17161-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Thrift AP (2016) The epidemic of oesophageal carcinoma: where are we now? Cancer Epidemiol 41:88–95. https://doi.org/10.1016/j.canep.2016.01.013

    Article  PubMed  Google Scholar 

  59. Beydoun AS, Stabenau KA, Altman KW et al (2023) Cancer risk in Barrett’s esophagus: a clinical review. Int J Mol Sci 24(7):6018. https://doi.org/10.3390/ijms24076018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. McDonald SAC, Lavery D, Wright NA et al (2015) Barrett oesophagus: lessons on its origins from the lesion itself. Nat Rev Gastroenterol Hepatol 12(1):50–60. https://doi.org/10.1038/nrgastro.2014.181

    Article  PubMed  Google Scholar 

  61. Kendall BJ, Whiteman DC (2006) Temporal changes in the endoscopic frequency of new cases of Barrett’s esophagus in an Australian health region. Am J Gastroenterol 101(6):1178–1182. https://doi.org/10.1111/j.1572-0241.2006.00548.x

    Article  PubMed  Google Scholar 

  62. Spechler SJ, Souza RF (2014) Barrett’s esophagus. N Engl J Med 371(9):836–845. https://doi.org/10.1056/NEJMra1314704

    Article  CAS  PubMed  Google Scholar 

  63. Anaparthy R, Sharma P (2014) Progression of Barrett oesophagus: role of endoscopic and histological predictors. Nat Rev Gastroenterol Hepatol 11(9):525–534. https://doi.org/10.1038/nrgastro.2014.69

    Article  PubMed  Google Scholar 

  64. Liu X, Cheng Y, Abraham JM et al (2018) Modeling Wnt signaling by CRISPR-Cas9 genome editing recapitulates neoplasia in human Barrett epithelial organoids. Cancer Lett 436:109–118. https://doi.org/10.1016/j.canlet.2018.08.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Kunze B, Wein F, Fang HY et al (2020) Notch signaling mediates differentiation in Barrett’s esophagus and promotes progression to adenocarcinoma. Gastroenterology 159(2):575–590. https://doi.org/10.1053/j.gastro.2020.04.033

    Article  CAS  PubMed  Google Scholar 

  66. Anand A, Fang HY, Mohammad-Shahi D et al (2021) Elimination of NF-κB signaling in vimentin+ stromal cells attenuates tumorigenesis in a mouse model of Barrett’s esophagus. Carcinogenesis 42(3):405–413. https://doi.org/10.1093/carcin/bgaa109

    Article  CAS  PubMed  Google Scholar 

  67. Nakagawa H, Whelan K, Lynch JP (2015) Mechanisms of Barrett’s oesophagus: intestinal differentiation, stem cells, and tissue models. Best Pract Res Clin Gastroenterol 29(1):3–16. https://doi.org/10.1016/j.bpg.2014.11.001

    Article  CAS  PubMed  Google Scholar 

  68. Jiang M, Li H, Zhang Y et al (2017) Transitional basal cells at the squamous-columnar junction generate Barrett’s oesophagus. Nature 550(7677):529–533. https://doi.org/10.1038/nature24269

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Nowicki-Osuch K, Zhuang L, Jammula S et al (2021) Molecular phenotyping reveals the identity of Barrett’s esophagus and its malignant transition. Science 373(6556):760–767. https://doi.org/10.1126/science.abd1449

    Article  CAS  PubMed  Google Scholar 

  70. Lee MH, Buterbaugh K, Richards-Kortum R et al (2012) Advanced endoscopic imaging for Barrett’s esophagus: current options and future directions. Curr Gastroenterol Rep 14(3):216–225. https://doi.org/10.1007/s11894-012-0259-3

    Article  PubMed  Google Scholar 

  71. Fang HY, Stangl S, Marcazzan S et al (2022) Targeted Hsp70 fluorescence molecular endoscopy detects dysplasia in Barrett’s esophagus. Eur J Nucl Med Mol Imaging 49(6):2049–2063. https://doi.org/10.1007/s00259-021-05582-y

    Article  CAS  PubMed  Google Scholar 

  72. Sahm V, Maurer C, Baumeister T et al (2022) Telomere shortening accelerates tumor initiation in the L2-IL1B mouse model of Barrett esophagus and emerges as a possible biomarker. Oncotarget 13:347–359. https://doi.org/10.18632/oncotarget.28198

  73. Lin Y, Totsuka Y, He Y et al (2013) Epidemiology of esophageal cancer in Japan and China. J Epidemiol 23(4):233–242. https://doi.org/10.2188/jea.je20120162

    Article  PubMed  Google Scholar 

  74. Liu K, Zhao T, Wang J et al (2019) Etiology, cancer stem cells and potential diagnostic biomarkers for esophageal cancer. Cancer Lett 458:21–28. https://doi.org/10.1016/j.canlet.2019.05.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Hayakawa Y, Nakagawa H, Rustgi AK et al (2021) Stem cells and origins of cancer in the upper gastrointestinal tract. Cell Stem Cell 28(8):1343–1361. https://doi.org/10.1016/j.stem.2021.05.012

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Natsuizaka M, Whelan KA, Kagawa S et al (2017) Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma. Nat Commun 8(1):1758. https://doi.org/10.1038/s41467-017-01500-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kajiwara C, Fumoto K, Kimura H et al (2018) p63-dependent Dickkopf3 expression promotes esophageal cancer cell proliferation via CKAP4. Cancer Res 78(21):6107–6120. https://doi.org/10.1158/0008-5472.CAN-18-1749

    Article  CAS  PubMed  Google Scholar 

  78. Tang Q, Lento A, Suzuki K et al (2021) Rab11-FIP1 mediates epithelial-mesenchymal transition and invasion in esophageal cancer. EMBO Rep 22(2):e48351. https://doi.org/10.15252/embr.201948351

  79. Wu Z, Zhou J, Zhang X et al (2021) Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nat Genet 53(6):881–894. https://doi.org/10.1038/s41588-021-00859-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Shimonosono M, Tanaka K, Flashner S et al (2021) Alcohol metabolism enriches squamous cell carcinoma cancer stem cells that survive oxidative stress via autophagy. Biomolecules 11(10):1479. https://doi.org/10.3390/biom11101479

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Hruz P, Straumann A, Bussmann C et al (2011) Escalating incidence of eosinophilic esophagitis: a 20-year prospective, population-based study in Olten County, Switzerland. J Allergy Clin Immunol 128:1349–1350. https://doi.org/10.1016/j.jaci.2011.09.013

    Article  PubMed  Google Scholar 

  82. Attwood SE, Smyrk TC, Demeester TR et al (1993) Esophageal eosinophilia with dysphagia. A distinct clinicopathologic syndrome. Dig Dis Sci 38(1):109–116. https://doi.org/10.1007/BF01296781

  83. Dellon ES, Liacouras CA (2014) Advances in clinical management of eosinophilic esophagitis. Gastroenterology 147(6):1238–1254. https://doi.org/10.1053/j.gastro.2014.07.055

    Article  PubMed  Google Scholar 

  84. Muir A, Falk GW (2021) Eosinophilic esophagitis: a review. JAMA 326(13):1310–1318. https://doi.org/10.1001/jama.2021.14920

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Navarro P, Arias Á, Arias-González L, Laserna-Mendieta EJ, Ruiz-Ponce M, Lucendo AJ (2019) Systematic review with meta-analysis: the growing incidence and prevalence of eosinophilic oesophagitis in children and adults in population-based studies. Aliment Pharmacol Ther 49(9):1116–1125. https://doi.org/10.1111/apt.15231

    Article  PubMed  Google Scholar 

  86. Whelan KA, Merves JF, Giroux V et al (2017) Autophagy mediates epithelial cytoprotection in eosinophilic oesophagitis. Gut 66(7):1197–1207. https://doi.org/10.1136/gutjnl-2015-310341

    Article  CAS  PubMed  Google Scholar 

  87. Nakagawa H, Kasagi Y, Karakasheva TA et al (2020) Modeling epithelial homeostasis and reactive epithelial changes in human and murine three-dimensional esophageal organoids. Curr Protoc Stem Cell Biol 52(1):e106. https://doi.org/10.1002/cpsc.106

  88. Kaymak T, Kaya B, Wuggenig P et al (2022) IL-20 subfamily cytokines impair the oesophageal epithelial barrier by diminishing filaggrin in eosinophilic oesophagitis. Gut. https://doi.org/10.1136/gutjnl-2022-327166

    Article  PubMed  Google Scholar 

  89. Akdis CA (2021) Does the epithelial barrier hypothesis explain the increase in allergy, autoimmunity and other chronic conditions? Nat Rev Immunol 21(11):739–751. https://doi.org/10.1038/s41577-021-00538-7

    Article  CAS  PubMed  Google Scholar 

  90. Doyle AD, Masuda MY, Pyon GC et al (2023) Detergent exposure induces epithelial barrier dysfunction and eosinophilic inflammation in the esophagus. Allergy 78(1):192–201. https://doi.org/10.1111/all.15457

    Article  CAS  PubMed  Google Scholar 

  91. Hara T, Kasagi Y, Wang J et al (2022) CD73+ epithelial progenitor cells that contribute to homeostasis and renewal are depleted in eosinophilic esophagitis. Cell Mol Gastroenterol Hepatol 13(5):1449–1467. https://doi.org/10.1016/j.jcmgh.2022.01.018

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. van Lennep M, Singendonk MMJ, Dall’Oglio L et al (2019) Oesophageal atresia Nat Rev Dis Primers 5(1):26. https://doi.org/10.1038/s41572-019-0077-0

    Article  PubMed  Google Scholar 

  93. Spitz L, Kiely E, Pierro A (2004) Gastric transposition in children–a 21-year experience. J Pediatr Surg 39(3):276–281. https://doi.org/10.1016/j.jpedsurg.2003.11.032

    Article  PubMed  Google Scholar 

  94. Hamza AF, Abdelhay S, Sherif H et al (2003) Caustic esophageal strictures in children: 30 years’ experience. J Pediatr Surg 38(6):828–833. https://doi.org/10.1016/s0022-3468(03)00105-2

    Article  PubMed  Google Scholar 

  95. Bax NM, van der Zee DC (2007) Jejunal pedicle grafts for reconstruction of the esophagus in children. J Pediatr Surg 42(2):363–369. https://doi.org/10.1016/j.jpedsurg.2006.10.009

    Article  CAS  PubMed  Google Scholar 

  96. Spitz L (2007) Oesophageal atresia. Orphanet J Rare Dis 2:24. https://doi.org/10.1186/1750-1172-2-24

    Article  PubMed  PubMed Central  Google Scholar 

  97. Low DE (2011) Update on staging and surgical treatment options for esophageal cancer. J Gastrointest Surg 15:719. https://doi.org/10.1007/s11605-011-1515-9

    Article  PubMed  Google Scholar 

  98. Spurrier RG, Speer AL, Hou X et al (2015) Murine and human tissue-engineered esophagus form from sufficient stem/progenitor cells and do not require microdesigned biomaterials. Tissue Eng Part A 21(5–6):906–915. https://doi.org/10.1089/ten.TEA.2014.0357

    Article  CAS  PubMed  Google Scholar 

  99. Trecartin A, Danopoulos S, Spurrier R et al (2016) Establishing proximal and distal regional identities in murine and human tissue-engineered lung and trachea. Tissue Eng Part C Methods 22(11):1049–1057. https://doi.org/10.1089/ten.TEC.2016.0261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Finkbeiner SR, Freeman JJ, Wieck MM et al (2015) Generation of tissue-engineered small intestine using embryonic stem cell-derived human intestinal organoids. Biol Open 4(11):1462–1472. https://doi.org/10.1242/bio.013235

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Liu C, Qin T, Huang Y et al (2020) Drug screening model meets cancer organoid technology. Transl Oncol 13(11):100840. https://doi.org/10.1016/j.tranon.2020.100840

  102. Baker EJ, Beck NA, Berg EL et al (2019) Advancing nonclinical innovation and safety in pharmaceutical testing. Drug Discov Today 24(2):624–628. https://doi.org/10.1016/j.drudis.2018.11.011

    Article  PubMed  Google Scholar 

  103. Caponigro G, Sellers WR (2011) Advances in the preclinical testing of cancer therapeutic hypotheses. Nat Rev Drug Discov 10(3):179–187. https://doi.org/10.1038/nrd3385

    Article  CAS  PubMed  Google Scholar 

  104. Derouet MF, Allen J, Wilson GW et al (2020) Towards personalized induction therapy for esophageal adenocarcinoma: organoids derived from endoscopic biopsy recapitulate the pre-treatment tumor. Sci Rep 10(1):14514. https://doi.org/10.1038/s41598-020-71589-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Shapiro J, van Lanschot JJB, Hulshof MCCM et al (2015) Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol 16:1090–1098. https://doi.org/10.1016/S1470-2045(15)00040-6

    Article  PubMed  Google Scholar 

  106. Eyck BM, van Lanschot JJB, Hulshof MCCM et al (2021) 10-year outcome of a randomized trial comparing neoadjuvant chemoradiotherapy and surgery with surgery alone for esophageal cancer (CROSS trial). Eur J Surg Oncol 47:e31. https://doi.org/10.1200/JCO.20.03614

  107. Dings MPG, van der Zalm AP, Bootsma S et al (2022) Estrogen-related receptor alpha drives mitochondrial biogenesis and resistance to neoadjuvant chemoradiation in esophageal cancer. Cell Rep Med 3(11):100802. https://doi.org/10.1016/j.xcrm.2022.100802

  108. Driehuis E, Kolders S, Spelier S et al (2019) Oral mucosal organoids as a potential platform for personalized cancer therapy. Cancer Discov 9(7):852–871. https://doi.org/10.1158/2159-8290.CD-18-1522

    Article  CAS  PubMed  Google Scholar 

  109. Driehuis E, Kretzschmar K, Clevers H (2020) Establishment of patient-derived cancer organoids for drug-screening applications. Nat Protoc 15(10):3380–3409. https://doi.org/10.1038/s41596-020-0379-4

    Article  CAS  PubMed  Google Scholar 

  110. Karakasheva TA, Gabre JT, Sachdeva UM et al (2021) Patient-derived organoids as a platform for modeling a patient’s response to chemoradiotherapy in esophageal cancer. Sci Rep 11(1):21304. https://doi.org/10.1038/s41598-021-00706-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Zhou Z, Cong L, Cong X (2021) Patient-derived organoids in precision medicine: drug screening, organoid-on-a-chip and living organoid biobank. Front Oncol 11:762184. Patient-Derived Organoids in Precision Medicine: Drug Screening, Organoid-on-a-Chip and Living Organoid Biobank

  112. Kawasaki K, Toshimitsu K, Matano M et al (2020) An organoid biobank of neuroendocrine neoplasms enables genotype-phenotype mapping. Cell 183(5):1420–1435.e21. https://doi.org/10.1016/j.cell.2020.10.023

    Article  CAS  PubMed  Google Scholar 

  113. Nanki K, Toshimitsu K, Takano A et al (2018) Divergent routes toward Wnt and R-spondin niche independency during human gastric carcinogenesis. Cell 174(4):856–869.e17. https://doi.org/10.1016/j.cell.2018.07.027

    Article  CAS  PubMed  Google Scholar 

  114. Pauli C, Hopkins BD, Prandi D et al (2017) Personalized in vitro and in vivo cancer models to guide precision medicine. Cancer Discov 7(5):462–477. https://doi.org/10.1158/2159-8290.CD-16-1154

    Article  PubMed  PubMed Central  Google Scholar 

  115. Wörsdörfer P, I T, Asahina I, et al (2020) Do not keep it simple: recent advances in the generation of complex organoids. J Neural Transm (Vienna) 127(11):1569–1577. https://doi.org/10.1007/s00702-020-02198-8

    Article  PubMed  Google Scholar 

  116. Ma C, Peng Y, Li H et al (2021) Organ-on-a-chip: a new paradigm for drug development. Trends Pharmacol Sci 42(2):119–133. https://doi.org/10.1016/j.tips.2020.11.009

    Article  CAS  PubMed  Google Scholar 

  117. Trujillo-de Santiago G, Flores-Garza BG, Tavares-Negrete JA et al (2019) The tumor-on-chip: recent advances in the development of microfluidic systems to recapitulate the physiology of solid tumors. Materials (Basel) 12(18):2945. https://doi.org/10.3390/ma12182945

    Article  CAS  PubMed  Google Scholar 

  118. Cherne MD, Sidar B, Sebrell TA et al (2021) A synthetic hydrogel, VitroGel® ORGANOID-3, improves immune cell-epithelial interactions in a tissue chip co-culture model of human gastric organoids and dendritic cells. Front Pharmacol 12:707891. https://doi.org/10.3389/fphar.2021.707891

  119. Lu S, Cuzzucoli F, Jiang J et al (2018) Development of a biomimetic liver tumor-on-a-chip model based on decellularized liver matrix for toxicity testing. Lab Chip 18(22):3379–3392. https://doi.org/10.1039/c8lc00852c

    Article  CAS  PubMed  Google Scholar 

  120. Chen L, Wei X, Gu D et al (2023) Human liver cancer organoids: biological applications, current challenges, and prospects in hepatoma therapy. Cancer Lett 555:216048. https://doi.org/10.1016/j.canlet.2022.216048

  121. Wang E, Xiang K, Zhang Y et al (2022) Patient-derived organoids (PDOs) and PDO-derived xenografts (PDOXs): new opportunities in establishing faithful pre-clinical cancer models. J Natl Cancer Cent 2(4):263–276. https://doi.org/10.1016/j.jncc.2022.10.001

    Article  Google Scholar 

  122. Gao D, Vela I, Sboner A et al (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159(1):176–187. https://doi.org/10.1016/j.cell.2014.08.016

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Fujii M, Shimokawa M, Date S et al (2016) A colorectal tumor organoid library demonstrates progressive loss of niche factor requirements during tumorigenesis. Cell Stem Cell 18(6):827–838. https://doi.org/10.1016/j.stem.2016.04.003

    Article  CAS  PubMed  Google Scholar 

  124. Lai Y, Wei X, Lin S et al (2017) Current status and perspectives of patient-derived xenograft models in cancer research. J Hematol Oncol 10(1):106. https://doi.org/10.1186/s13045-017-0470-7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Bleijs M, van de Wetering M, Clevers H et al (2019). Xenograft and organoid model systems in cancer research. EMBO J 38(15):e101654. https://doi.org/10.15252/embj.2019101654

  126. Lee SH, Hu W, Matulay JT et al (2018) Tumor evolution and drug response in patient-derived organoid models of bladder cancer. Cell 173(2):515–528.e17. https://doi.org/10.1016/j.cell.2018.03.017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This work was supported by National Science Foundation of China  (No.82271595) and Shanghai Jiao Tong University School of Medicine 16th College Students’ Innovative Training Program.

Author information

Authors and Affiliations

  1. Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Hongyuan Liu

  2. Shanghai Jiao Tong University, School of Public Health, Shanghai, 200025, China

    Xianli Wang

Authors
  1. Hongyuan Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xianli Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Hongyuan Liu contributed to the idea of this review, performed the literature search, and drafted the article. Xianli Wang provided instructions and critically revised the work.

Corresponding author

Correspondence to Xianli Wang.

Ethics declarations

Ethics approval

Not applicable.

Consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, H., Wang, X. Esophageal organoids: applications and future prospects. J Mol Med 101, 931–945 (2023). https://doi.org/10.1007/s00109-023-02340-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00109-023-02340-5

Keywords

Search

Navigation