1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

New Age Strategies To Reconstruct Mucosal Tissue Colonization and Growth in Cell Culture Systems

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy this Microbiology Spectrum Article
Price Non-Member $15.00
  • Authors: Alyssa C. Fasciano1, Joan Mecsas3, Ralph R. Isberg4
  • Editors: Pascale Cossart5, Craig R. Roy6, Philippe Sansonetti7
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA; 2: Program in Immunology, Sackler School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA; 3: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA; 4: Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, MA; 5: Institut Pasteur, Paris, France; 6: Yale University School of Medicine, New Haven, Connecticut; 7: Institut Pasteur, Paris, France
  • Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0013-2019
  • Received 23 July 2018 Accepted 10 January 2019 Published 08 March 2019
  • Ralph R. Isberg, [email protected]
image of New Age Strategies To Reconstruct Mucosal Tissue Colonization and Growth in Cell Culture Systems
    Preview this microbiology spectrum article:
    Zoom in
    Zoomout

    New Age Strategies To Reconstruct Mucosal Tissue Colonization and Growth in Cell Culture Systems, Page 1 of 2

    | /docserver/preview/fulltext/microbiolspec/7/2/BAI-0013-2019-1.gif /docserver/preview/fulltext/microbiolspec/7/2/BAI-0013-2019-2.gif
  • Abstract:

    Over the past few decades, cell culture systems have greatly expanded our understanding of host-pathogen interactions. However, studies using these models have been limited by the fact that they lack the complexity of the human body. Therefore, recent efforts that allow tissue architecture to be mimicked during culture have included the development of methods and technology that incorporate tissue structure, cellular composition, and efficient long-term culture. These advances have opened the door for the study of pathogens that previously could not be cultured and for the study of pathophysiological properties of infection that could not be easily elucidated using traditional culture models. Here we discuss the latest studies using organoids and engineering technology that have been developed and applied to the study of host-pathogen interactions in mucosal tissues.

  • Citation: Fasciano A, Mecsas J, Isberg R. 2019. New Age Strategies To Reconstruct Mucosal Tissue Colonization and Growth in Cell Culture Systems. Microbiol Spectrum 7(2):BAI-0013-2019. doi:10.1128/microbiolspec.BAI-0013-2019.

References

1. Falkow S. 2004. Molecular Koch’s postulates applied to bacterial pathogenicity—a personal recollection 15 years later. Nat Rev Microbiol 2:67–72 http://dx.doi.org/10.1038/nrmicro799. [PubMed]
2. Mestas J, Hughes CC. 2004. Of mice and not men: differences between mouse and human immunology. J Immunol 172:2731–2738 http://dx.doi.org/10.4049/jimmunol.172.5.2731. [PubMed]
3. Rall GF, Lawrence DM, Patterson CE. 2000. The application of transgenic and knockout mouse technology for the study of viral pathogenesis. Virology 271:220–226 http://dx.doi.org/10.1006/viro.2000.0337. [PubMed]
4. Falkow S, Isberg RR, Portnoy DA. 1992. The interaction of bacteria with mammalian cells. Annu Rev Cell Biol 8:333–363 http://dx.doi.org/10.1146/annurev.cb.08.110192.002001. [PubMed]
5. Cossart P. 1997. Host/pathogen interactions. Subversion of the mammalian cell cytoskeleton by invasive bacteria. J Clin Invest 99:2307–2311 http://dx.doi.org/10.1172/JCI119409. [PubMed]
6. Falkow S. 1991. Bacterial entry into eukaryotic cells. Cell 65:1099–1102 http://dx.doi.org/10.1016/0092-8674(91)90003-H.
7. Kazmierczak BI, Mostov K, Engel JN. 2001. Interaction of bacterial pathogens with polarized epithelium. Annu Rev Microbiol 55:407–435 http://dx.doi.org/10.1146/annurev.micro.55.1.407. [PubMed]
8. Sun H, Chow EC, Liu S, Du Y, Pang KS. 2008. The Caco-2 cell monolayer: usefulness and limitations. Expert Opin Drug Metab Toxicol 4:395–411 http://dx.doi.org/10.1517/17425255.4.4.395. [PubMed]
9. Hidalgo IJ, Raub TJ, Borchardt RT. 1989. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability. Gastroenterology 96:736–749 http://dx.doi.org/10.1016/0016-5085(89)90897-4.
10. Grainger CI, Greenwell LL, Lockley DJ, Martin GP, Forbes B. 2006. Culture of Calu-3 cells at the air interface provides a representative model of the airway epithelial barrier. Pharm Res 23:1482–1490 http://dx.doi.org/10.1007/s11095-006-0255-0. [PubMed]
11. McCormick BA. 2003. The use of transepithelial models to examine host-pathogen interactions. Curr Opin Microbiol 6:77–81 http://dx.doi.org/10.1016/S1369-5274(02)00003-6.
12. Abbott A. 2003. Cell culture: biology’s new dimension. Nature 424:870–872 http://dx.doi.org/10.1038/424870a. [PubMed]
13. Evans GS, Flint N, Somers AS, Eyden B, Potten CS. 1992. The development of a method for the preparation of rat intestinal epithelial cell primary cultures. J Cell Sci 101:219–231. [PubMed]
14. Honegger P. 2001. Overview of cell and tissue culture techniques. Curr Protoc Pharmacol Chapter 12:Unit 12 1.
15. Lancaster MA, Knoblich JA. 2014. Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345:1247125 http://dx.doi.org/10.1126/science.1247125. [PubMed]
16. 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 15:701–706 http://dx.doi.org/10.1038/nm.1951. [PubMed]
17. 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 459:262–265 http://dx.doi.org/10.1038/nature07935. [PubMed]
18. Barker N, van Es JH, Kuipers J, Kujala P, van den Born M, Cozijnsen M, Haegebarth A, Korving J, Begthel H, Peters PJ, Clevers H. 2007. Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449:1003–1007 http://dx.doi.org/10.1038/nature06196. [PubMed]
19. 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. 2011. Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology 141:1762–1772 http://dx.doi.org/10.1053/j.gastro.2011.07.050. [PubMed]
20. McCracken KW, Howell JC, Wells JM, Spence JR. 2011. Generating human intestinal tissue from pluripotent stem cells in vitro. Nat Protoc 6:1920–1928 http://dx.doi.org/10.1038/nprot.2011.410. [PubMed]
21. 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 470:105–109 http://dx.doi.org/10.1038/nature09691. [PubMed]
22. Sinagoga KL, Wells JM. 2015. Generating human intestinal tissues from pluripotent stem cells to study development and disease. EMBO J 34:1149–1163 http://dx.doi.org/10.15252/embj.201490686. [PubMed]
23. Foulke-Abel J, In J, Yin J, Zachos NC, Kovbasnjuk O, Estes MK, de Jonge H, Donowitz M. 2016. Human enteroids as a model of upper small intestinal ion transport physiology and pathophysiology. Gastroenterology 150:638–649.e8 http://dx.doi.org/10.1053/j.gastro.2015.11.047. [PubMed]
24. Hill DR, Huang S, Tsai YH, Spence JR, Young VB. 2017. Real-time measurement of epithelial barrier permeability in human intestinal organoids. J Vis Exp 2017:e56960 http://dx.doi.org/10.3791/56960.
25. 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 83:138–145 http://dx.doi.org/10.1128/IAI.02561-14. [PubMed]
26. Hill DR, Huang S, Nagy MS, Yadagiri VK, Fields C, Mukherjee D, Bons B, Dedhia PH, Chin AM, Tsai YH, Thodla S, Schmidt TM, Walk S, Young VB, Spence JR. 2017. Bacterial colonization stimulates a complex physiological response in the immature human intestinal epithelium. eLife 6:e29132 http://dx.doi.org/10.7554/eLife.29132. [PubMed]
27. VanDussen KL, Marinshaw JM, Shaikh N, Miyoshi H, Moon C, Tarr PI, Ciorba MA, Stappenbeck TS. 2015. Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Gut 64:911–920 http://dx.doi.org/10.1136/gutjnl-2013-306651. [PubMed]
28. In J, Foulke-Abel J, Zachos NC, Hansen AM, Kaper JB, Bernstein HD, Halushka M, Blutt S, Estes MK, Donowitz M, Kovbasnjuk O. 2016. Enterohemorrhagic Escherichia coli reduce mucus and intermicrovillar bridges in human stem cell-derived colonoids. Cell Mol Gastroenterol Hepatol 2:48–62.e3 http://dx.doi.org/10.1016/j.jcmgh.2015.10.001. [PubMed]
29. Duizer E, Schwab KJ, Neill FH, Atmar RL, Koopmans MP, Estes MK. 2004. Laboratory efforts to cultivate noroviruses. J Gen Virol 85:79–87 http://dx.doi.org/10.1099/vir.0.19478-0. [PubMed]
30. Papafragkou E, Hewitt J, Park GW, Greening G, Vinjé J. 2013. Challenges of culturing human norovirus in three-dimensional organoid intestinal cell culture models. PLoS One 8:e63485 http://dx.doi.org/10.1371/journal.pone.0063485. [PubMed]
31. Wobus CE, Thackray LB, Virgin HW IV. 2006. Murine norovirus: a model system to study norovirus biology and pathogenesis. J Virol 80:5104–5112 http://dx.doi.org/10.1128/JVI.02346-05. [PubMed]
32. 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 353:1387–1393 http://dx.doi.org/10.1126/science.aaf5211. [PubMed]
33. Zhang D, Tan M, Zhong W, Xia M, Huang P, Jiang X. 2017. Human intestinal organoids express histo-blood group antigens, bind norovirus VLPs, and support limited norovirus replication. Sci Rep 7:12621 http://dx.doi.org/10.1038/s41598-017-12736-2. [PubMed]
34. Finkbeiner SR, Zeng XL, Utama B, Atmar RL, Shroyer NF, Estes MK. 2012. Stem cell-derived human intestinal organoids as an infection model for rotaviruses. mBio 3:e00159-12 http://dx.doi.org/10.1128/mBio.00159-12. [PubMed]
35. 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 90:43–56 http://dx.doi.org/10.1128/JVI.01930-15.
36. Saxena K, Simon LM, Zeng XL, Blutt SE, Crawford SE, Sastri NP, Karandikar UC, Ajami NJ, Zachos NC, Kovbasnjuk O, Donowitz M, Conner ME, Shaw CA, Estes MK. 2017. A paradox of transcriptional and functional innate interferon responses of human intestinal enteroids to enteric virus infection. Proc Natl Acad Sci USA 114:E570–E579 http://dx.doi.org/10.1073/pnas.1615422114. [PubMed]
37. Yin Y, Bijvelds M, Dang W, Xu L, van der Eijk AA, Knipping K, Tuysuz N, Dekkers JF, Wang Y, de Jonge J, Sprengers D, van der Laan LJ, Beekman JM, Ten Berge D, Metselaar HJ, de Jonge H, Koopmans MP, Peppelenbosch MP, Pan Q. 2015. Modeling rotavirus infection and antiviral therapy using primary intestinal organoids. Antiviral Res 123:120–31 http://dx.doi.org/10.1016/j.antiviral.2015.09.010. [PubMed]
38. Middendorp S, Schneeberger K, Wiegerinck CL, Mokry M, Akkerman RD, van Wijngaarden S, Clevers H, Nieuwenhuis EE. 2014. Adult stem cells in the small intestine are intrinsically programmed with their location-specific function. Stem Cells 32:1083–1091 http://dx.doi.org/10.1002/stem.1655. [PubMed]
39. Holly MK, Smith JG. 2018. Adenovirus infection of human enteroids reveals interferon sensitivity and preferential infection of goblet cells. J Virol 92:e00250-18 http://dx.doi.org/10.1128/JVI.00250-18. [PubMed]
40. Drummond CG, Bolock AM, Ma C, Luke CJ, Good M, Coyne CB. 2017. Enteroviruses infect human enteroids and induce antiviral signaling in a cell lineage-specific manner. Proc Natl Acad Sci USA 114:1672–1677 http://dx.doi.org/10.1073/pnas.1617363114. [PubMed]
41. Rajan A, Vela L, Zeng XL, Yu X, Shroyer N, Blutt SE, Poole NM, Carlin LG, Nataro JP, Estes MK, Okhuysen PC, Maresso AW. 2018. Novel segment- and host-specific patterns of enteroaggregative Escherichia coli adherence to human intestinal enteroids. mBio 9:e02419-17 http://dx.doi.org/10.1128/mBio.02419-17. [PubMed]
42. Karve SS, Pradhan S, Ward DV, Weiss AA. 2017. Intestinal organoids model human responses to infection by commensal and Shiga toxin producing Escherichia coli. PLoS One 12:e0178966 http://dx.doi.org/10.1371/journal.pone.0178966. [PubMed]
43. 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. ERRATUM Sci Rep 7:46790 http://dx.doi.org/10.1038/srep45270. [PubMed]
44. Willet SG, Mills JC. 2016. Stomach organ and cell lineage differentiation: from embryogenesis to adult homeostasis. Cell Mol Gastroenterol Hepatol 2:546–559 http://dx.doi.org/10.1016/j.jcmgh.2016.05.006. [PubMed]
45. 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 148:126–136 e6.
46. Bartfeld S, Clevers H. 2015. Organoids as model for infectious diseases: culture of human and murine stomach organoids and microinjection of Helicobacter pylori. J Vis Exp (105) : http://dx.doi.org/10.3791/53359.
47. 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 516:400–404 http://dx.doi.org/10.1038/nature13863. [PubMed]
48. Schlaermann P, Toelle B, Berger H, Schmidt SC, Glanemann M, Ordemann J, Bartfeld S, Mollenkopf HJ, Meyer TF. 2016. A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro. Gut 65:202–213 http://dx.doi.org/10.1136/gutjnl-2014-307949. [PubMed]
49. Huang JY, Sweeney EG, Sigal M, Zhang HC, Remington SJ, Cantrell MA, Kuo CJ, Guillemin K, Amieva MR. 2015. Chemodetection and destruction of host urea allows Helicobacter pylori to locate the epithelium. Cell Host Microbe 18:147–156 http://dx.doi.org/10.1016/j.chom.2015.07.002. [PubMed]
50. Bhatia SN, Ingber DE. 2014. Microfluidic organs-on-chips. Nat Biotechnol 32:760–772 http://dx.doi.org/10.1038/nbt.2989. [PubMed]
51. Franks TJ, Colby TV, Travis WD, Tuder RM, Reynolds HY, Brody AR, Cardoso WV, Crystal RG, Drake CJ, Engelhardt J, Frid M, Herzog E, Mason R, Phan SH, Randell SH, Rose MC, Stevens T, Serge J, Sunday ME, Voynow JA, Weinstein BM, Whitsett J, Williams MC. 2008. Resident cellular components of the human lung: current knowledge and goals for research on cell phenotyping and function. Proc Am Thorac Soc 5:763–766 http://dx.doi.org/10.1513/pats.200803-025HR. [PubMed]
52. Huh D, Matthews BD, Mammoto A, Montoya-Zavala M, Hsin HY, Ingber DE. 2010. Reconstituting organ-level lung functions on a chip. Science 328:1662–1668 http://dx.doi.org/10.1126/science.1188302. [PubMed]
53. Benam KH, Novak R, Nawroth J, Hirano-Kobayashi M, Ferrante TC, Choe Y, Prantil-Baun R, Weaver JC, Bahinski A, Parker KK, Ingber DE. 2016. Matched-comparative modeling of normal and diseased human airway responses using a microengineered breathing lung chip. Cell Syst 3:456–466.E4 http://dx.doi.org/10.1016/j.cels.2016.10.003. [PubMed]
54. Benam KH, Villenave R, Lucchesi C, Varone A, Hubeau C, Lee HH, Alves SE, Salmon M, Ferrante TC, Weaver JC, Bahinski A, Hamilton GA, Ingber DE. 2016. Small airway-on-a-chip enables analysis of human lung inflammation and drug responses in vitro. Nat Methods 13:151–157 http://dx.doi.org/10.1038/nmeth.3697. [PubMed]
55. Blume C, Reale R, Held M, Millar TM, Collins JE, Davies DE, Morgan H, Swindle EJ. 2015. Temporal monitoring of differentiated human airway epithelial cells using microfluidics. PLoS One 10:e0139872 http://dx.doi.org/10.1371/journal.pone.0139872. [PubMed]
56. Barkauskas CE, Chung MI, Fioret B, Gao X, Katsura H, Hogan BL. 2017. Lung organoids: current uses and future promise. Development 144:986–997 http://dx.doi.org/10.1242/dev.140103. [PubMed]
57. Chen YW, Huang SX, de Carvalho ALRT, Ho SH, Islam MN, Volpi S, Notarangelo LD, Ciancanelli M, Casanova JL, Bhattacharya J, Liang AF, Palermo LM, Porotto M, Moscona A, Snoeck HW. 2017. A three-dimensional model of human lung development and disease from pluripotent stem cells. Nat Cell Biol 19:542–549 http://dx.doi.org/10.1038/ncb3510. [PubMed]
58. van der Sanden SMG, Sachs N, Koekkoek SM, Koen G, Pajkrt D, Clevers H, Wolthers KC. 2018. Enterovirus 71 infection of human airway organoids reveals VP1-145 as a viral infectivity determinant. Emerg Microbes Infect 7:84 http://dx.doi.org/10.1038/s41426-018-0077-2. [PubMed]
59. Kim HJ, Huh D, Hamilton G, Ingber DE. 2012. Human gut-on-a-chip inhabited by microbial flora that experiences intestinal peristalsis-like motions and flow. Lab Chip 12:2165–2174 http://dx.doi.org/10.1039/c2lc40074j. [PubMed]
60. Gayer CP, Basson MD. 2009. The effects of mechanical forces on intestinal physiology and pathology. Cell Signal 21:1237–1244 http://dx.doi.org/10.1016/j.cellsig.2009.02.011. [PubMed]
61. Kim HJ, Ingber DE. 2013. Gut-on-a-chip microenvironment induces human intestinal cells to undergo villus differentiation. Integr Biol 5:1130–1140 http://dx.doi.org/10.1039/c3ib40126j. [PubMed]
62. Kim HJ, Li H, Collins JJ, Ingber DE. 2016. Contributions of microbiome and mechanical deformation to intestinal bacterial overgrowth and inflammation in a human gut-on-a-chip. Proc Natl Acad Sci USA 113:E7–E15 http://dx.doi.org/10.1073/pnas.1522193112. [PubMed]
63. Villenave R, Wales SQ, Hamkins-Indik T, Papafragkou E, Weaver JC, Ferrante TC, Bahinski A, Elkins CA, Kulka M, Ingber DE. 2017. Human gut-on-a-chip supports polarized infection of coxsackie B1 virus in vitro. PLoS One 12:e0169412 http://dx.doi.org/10.1371/journal.pone.0169412. [PubMed]
64. Bein A, Shin W, Jalili-Firoozinezhad S, Park MH, Sontheimer-Phelps A, Tovaglieri A, Chalkiadaki A, Kim HJ, Ingber DE. 2018. Microfluidic organ-on-a-chip models of human intestine. Cell Mol Gastroenterol Hepatol 5:659–668 http://dx.doi.org/10.1016/j.jcmgh.2017.12.010. [PubMed]
65. Chen Y, Lin Y, Davis KM, Wang Q, Rnjak-Kovacina J, Li C, Isberg RR, Kumamoto CA, Mecsas J, Kaplan DL. 2015. Robust bioengineered 3D functional human intestinal epithelium. Sci Rep 5:13708 http://dx.doi.org/10.1038/srep13708. [PubMed]
66. Shaban L, Chen Y, Fasciano AC, Lin Y, Kaplan DL, Kumamoto CA, Mecsas J. 2018. A 3D intestinal tissue model supports Clostridioides difficile germination, colonization, toxin production and epithelial damage. Anaerobe 50:85–92 http://dx.doi.org/10.1016/j.anaerobe.2018.02.006. [PubMed]
67. Zhou W, Chen Y, Roh T, Lin Y, Ling S, Zhao S, Lin JD, Khalil N, Cairns DM, Manousiouthakis E, Tse M, Kaplan DL. 2018. Multifunctional bioreactor system for human intestine tissues. ACS Biomater Sci Eng 4:231–239 http://dx.doi.org/10.1021/acsbiomaterials.7b00794. [PubMed]
68. Chen Y, Zhou W, Roh T, Estes MK, Kaplan DL. 2017. In vitro enteroid-derived three-dimensional tissue model of human small intestinal epithelium with innate immune responses. PLoS One 12:e0187880 http://dx.doi.org/10.1371/journal.pone.0187880. [PubMed]
69. Kasendra M, Tovaglieri A, Sontheimer-Phelps A, Jalili-Firoozinezhad S, Bein A, Chalkiadaki A, Scholl W, Zhang C, Rickner H, Richmond CA, Li H, Breault DT, Ingber DE. 2018. Development of a primary human small intestine-on-a-chip using biopsy-derived organoids. Sci Rep 8:2871 http://dx.doi.org/10.1038/s41598-018-21201-7. [PubMed]
Loading

Article metrics loading...

/content/journal/microbiolspec/10.1128/microbiolspec.BAI-0013-2019
2019-03-08
2019-06-17

Abstract:

Over the past few decades, cell culture systems have greatly expanded our understanding of host-pathogen interactions. However, studies using these models have been limited by the fact that they lack the complexity of the human body. Therefore, recent efforts that allow tissue architecture to be mimicked during culture have included the development of methods and technology that incorporate tissue structure, cellular composition, and efficient long-term culture. These advances have opened the door for the study of pathogens that previously could not be cultured and for the study of pathophysiological properties of infection that could not be easily elucidated using traditional culture models. Here we discuss the latest studies using organoids and engineering technology that have been developed and applied to the study of host-pathogen interactions in mucosal tissues.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Figures

Image of FIGURE 1
FIGURE 1

Methods for using intestinal organoids to study host-pathogen interactions. () Image of undifferentiated intestinal cysts containing stem cells. () (Left) Cysts can be differentiated in Matrigel and used for microinjection with bacteria. (Right) Image of differentiated enteroids. () (Left) Cysts can be broken up enzymatically with trypsin, seeded on Transwell filters, and differentiated into a polarized monolayer with an apical side (A) and a basolateral side (B). Microbes can be added to the apical side using a pipette. (Right) Apical surface of the monolayer. All images were taken with a 4× objective lens on an optical microscope.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0013-2019
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2
FIGURE 2

Method for development of a 3D silk scaffold to model human intestines. Reprinted from reference 65 under the CC BY 4.0 license.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0013-2019
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 3
FIGURE 3

Method for development of the intestine chip using enteroids to model human intestines. Reprinted from reference 69 under the CC BY 4.0 license.

Source: microbiolspec March 2019 vol. 7 no. 2 doi:10.1128/microbiolspec.BAI-0013-2019
Permissions and Reprints Request Permissions
Download as Powerpoint

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error