Intestinal organoid as an in vitromodel in studying host-microbial interactions
Received date: 11 Nov 2016
Accepted date: 15 Jan 2017
Published date: 17 Apr 2017
Copyright
BACKGROUND: Organoid is an in vitro three-dimensional organ-bud that shows realistic microanatomy and physiological relevance. The progress in generating organoids that faithfully recapitulate humanin vivo tissue composition has extended organoid applications from being just a basic research tool to a translational platform with a wide range of uses. Study of host-microbial interactions relies on model systems to mimic thein vivo infection. Researchers have developed various experimental models in vitro and in vivo to examine the dynamic host-microbial interactions. For some infectious pathogens, model systems are lacking whereas some of the used systems are far from optimal.
OBJECTIVE: In the present work, we will review the brief history and recent findings using organoids for studying host-microbial interactions.
METHODS: A systematic literature search was performed using the PubMed search engine. We also shared our data and research contribution to the field.
RESULTS: we summarize the brief history of 3D organoids. We discuss the feasibility of using organoids in studying host-microbial interactions, focusing on the development of intestinal organoids and gastric organoids. We highlight the advantage and challenges of the new experimental models. Further, we discuss the future direction in using organoids in studying host-microbial interactions and its potential application in biomedical studies.
CONCLUSION: In combination with genetic, transcriptome and proteomic profiling, both murine- and human-derived organoids have revealed crucial aspects of development, homeostasis and diseases. Specifically, human organoids from susceptible host will be used to test their responses to pathogens, probiotics, and drugs. Organoid system is an exciting tool for studying infectious disease, microbiome, and therapy.
Jun Sun . Intestinal organoid as an in vitromodel in studying host-microbial interactions[J]. Frontiers in Biology, 2017 , 12(2) : 94 -102 . DOI: 10.1007/s11515-017-1444-4
1 |
Aoki-Yoshida A, Saito S, Fukiya S , Aoki R, Takayama Y, Suzuki C , Sonoyama K (2016). Lactobacillus rhamnosus GG increases Toll-like receptor 3 gene expression in murine small intestine ex vivo and in vivo. Benef Microbes, 7(3): 421–429
|
2 |
Arnold J W, Roach J, Azcarate-Peril M A (2016). Emerging technologies for gut microbiome research. Trends Microbiol, 24(11): 887–901
|
3 |
Barrandon Y, Green H (1987). Three clonal types of keratinocyte with different capacities for multiplication. Proc Natl Acad Sci USA, 84(8): 2302–2306
|
4 |
Bartfeld S, Bayram T, van de Wetering M, Huch M , Begthel H , Kujala P , Vries R , Peters P J , Clevers H (2015). In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology, 148(1): 126–136.e6
|
5 |
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, 43(105):816–818
|
6 |
Bertaux-Skeirik N, Feng R, Schumacher M A , Li J, Mahe M M, Engevik A C, Javier J E, Peek R M Jr, Ottemann K, Orian-Rousseau V , Boivin G P , Helmrath M A , Zavros Y (2015). CD44 plays a functional role in Helicobacter pylori-induced epithelial cell proliferation. PLoS Pathog, 11(2): e1004663
|
7 |
Crosnier C, Stamataki D, Lewis J (2006). Organizing cell renewal in the intestine: stem cells, signals and combinatorial control. Nat Rev Genet, 7(5): 349–359
|
8 |
D’Aiuto L, Di Maio R, Heath B , Raimondi G , Milosevic J , Watson A M , Bamne M , Parks W T , Yang L, Lin B, Miki T , Mich-Basso J D , Arav-Boger R , Sibille E , Sabunciyan S , Yolken R , Nimgaonkar V (2012). Human induced pluripotent stem cell-derived models to investigate human cytomegalovirus infection in neural cells. PLoS One, 7(11): e49700
|
9 |
Dedhia P H, Bertaux-Skeirik N, Zavros Y , Spence J R (2016). Organoid models of human gastrointestinal development and disease. Gastroenterology, 150(5): 1098–1112nbsp;PMID:26774180
|
10 |
Dingli D, Nowak M A (2006). Cancer biology: infectious tumour cells. Nature, 443(7107): 35–36
|
11 |
Engevik M A, Aihara E, Montrose M H , Shull G E , Hassett D J , Worrell R T (2013). Loss of NHE3 alters gut microbiota composition and influences Bacteroides thetaiotaomicron growth. Am J Physiol Gastrointest Liver Physiol, 305(10): G697–G711
|
12 |
Ettayebi K, Crawford S E, Murakami K, Broughman J R , Karandikar U , Tenge V R , Neill F H , Blutt S E , Zeng X L , Qu L, Kou B, Opekun A R , Burrin D , Graham D Y , Ramani S , Atmar R L , Estes M K (2016). Replication of human noroviruses in stem cell-derived human enteroids. Science, 353(6306): 1387–1393
|
13 |
Fang S B, Schüller S, Phillips A D
|
14 |
Fatehullah A, Tan S H, Barker N (2016). Organoids as an in vitro model of human development and disease. Nat Cell Biol, 18(3): 246–254
|
15 |
Finkbeiner S R , Zeng X L , Utama B , Atmar R L , Shroyer N F , Estes M K (2012). Stem cell-derived human intestinal organoids as an infection model for rotaviruses. MBio, 3(4): e00159–e12
|
16 |
Forbester J L , Goulding D ,
|
17 |
Forbester J L , 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
|
18 |
Foulke-Abel J, In J, Kovbasnjuk O , Zachos N C , Ettayebi K , Blutt S E , Hyser J M , Zeng X L , Crawford S E , Broughman J R , Estes M K , Donowitz M (2014). Human enteroids as an ex-vivo model of host-pathogen interactions in the gastrointestinal tract. Exp Biol Med (Maywood), 239(9): 1124–1134
|
19 |
Garcez P P, Loiola E C, Madeiro da Costa R, Higa L M , Trindade P , Delvecchio R , Nascimento J M , Brindeiro R , Tanuri A , Rehen S K (2016). Zika virus impairs growth in human neurospheres and brain organoids. Science, 352(6287): 816–818
|
20 |
Gjorevski N, Sachs N, Manfrin A , Giger S , Bragina M E , Ordóñez-Morán P, Clevers H , Lutolf M P (2016). Designer matrices for intestinal stem cell and organoid culture. Nature, 539(7630): 560–564
|
21 |
Harrison R G (1907). Observations on the living developing fiber. Proc Soc Exp Biol Med, 4(1): 140–143
|
22 |
Heuberger J, Kosel F, Qi J , Grossmann K S , Rajewsky K , Birchmeier W (2014). Shp2/MAPK signaling controls goblet/paneth cell fate decisions in the intestine. Proc Natl Acad Sci USA, 111(9): 3472–3477
|
23 |
Hilleman M R (1990). History, precedent, and progress in the development of mammalian cell culture systems for preparing vaccines: safety considerations revisited. J Med Virol, 31(1): 5–12
|
24 |
Huang G, Ye S, Zhou X , Liu D, Ying Q L (2015a). Molecular basis of embryonic stem cell self-renewal: from signaling pathways to pluripotency network. Cell Mol Life Sci, 72(9): 1741–1757
|
25 |
Huang J Y, Sweeney E G, Sigal M, Zhang H C , Remington S J , Cantrell M A , Kuo C J , Guillemin K , Amieva M R (2015b). Chemodetection and destruction of host urea allows Helicobacter pylori to locate the epithelium. Cell Host Microbe, 18(2): 147–156
|
26 |
Huch M, Koo B K (2015). Modeling mouse and human development using organoid cultures. Development, 142(18): 3113–3125
|
27 |
In J G, Foulke-Abel J, Estes M K , Zachos N C , Kovbasnjuk O , Donowitz M (2016). Human mini-guts: new insights into intestinal physiology and host-pathogen interactions. Nat Rev Gastroenterol Hepatol, 13(11): 633–642
|
28 |
Jung P, Sato T, Merlos-Suárez A, Barriga F M , Iglesias M , Rossell D , Auer H, Gallardo M, Blasco M A , Sancho E , Clevers H , Batlle E (2011). Isolation and in vitro expansion of human colonic stem cells. Nat Med, 17(10): 1225–1227
|
29 |
Klotz C, Aebischer T, Seeber F (2012). Stem cell-derived cell cultures and organoids for protozoan parasite propagation and studying host-parasite interaction. Int J Med Microbiol, 302(4-5): 203–209
|
30 |
Kristin W, Weitz J,
|
31 |
Leslie J L, Huang S, Opp J S , Nagy M S , Kobayashi M , Young V B , Spence J R (2015). Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect Immun, 83(1): 138–145
|
32 |
Mahe M M, Aihara E, Schumacher M A , Zavros Y , Montrose M H , Helmrath M A , Sato T, Shroyer N F (2013). Establishment of gastrointestinal epithelial organoids. Curr Protoc Mouse Biol, 3(4): 217–240
|
33 |
Mahe M M, Sundaram N, Watson C L , Shroyer N F , Helmrath M A (2015). Establishment of human epithelial enteroids and colonoids from whole tissue and biopsy. J Vis Exp, (97): e52483-e52483
|
34 |
McCracken K W , Catá E M , Crawford C M , Sinagoga K L , Schumacher M , Rockich B E , Tsai Y H , Mayhew C N , Spence J R , Zavros Y , Wells J M (2014). Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature, 516(7531): 400–404
|
35 |
Miyoshi H, Stappenbeck T S (2013). In vitro expansion and genetic modification of gastrointestinal stem cells in spheroid culture. Nat Protoc, 8(12): 2471–2482
|
36 |
Ng S, Schwartz R E, March S, Galstian A , Gural N , Shan J, Prabhu M, Mota M M , Bhatia S N (2015). Human iPSC-derived hepatocyte-like cells support Plasmodium liver-stage infection in vitro. Stem Cell Rep, 4(3): 348–359
|
37 |
Ootani A, Li X, Sangiorgi E , Ho Q T , Ueno H, Toda S, Sugihara H , Fujimoto K , Weissman I L , Capecchi M R , Kuo C J (2009). Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med, 15(6): 701–706
|
38 |
Penkert R R, Kalejta R F (2013). Human embryonic stem cell lines model experimental human cytomegalovirus latency. MBio, 4(3): e00298–e13
|
39 |
Roelandt P, Obeid S, Paeshuyse J , Vanhove J , Van Lommel A , Nahmias Y , Nevens F , Neyts J , Verfaillie C M (2012). Human pluripotent stem cell-derived hepatocytes support complete replication of hepatitis C virus. J Hepatol, 57(2): 246–251
|
40 |
Salama N R, Hartung M L, Müller A (2013). Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol, 11(6): 385–399
|
41 |
Sato T, Stange D E, Ferrante M, Vries R G , Van Es J H , Van den Brink S , Van Houdt W J , Pronk A , Van Gorp J , Siersema P D , Clevers H (2011a). Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett’s epithelium. Gastroenterology, 141(5): 1762–1772
|
42 |
Sato T, van Es J H, Snippert H J, Stange D E, Vries R G, van den Born M, Barker N , Shroyer N F , van de Wetering M , Clevers H (2011b). Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts. Nature, 469(7330): 415–418
|
43 |
Sato T, Vries R G, Snippert H J, van de Wetering M, Barker N , Stange D E , van Es J H , Abo A, Kujala P, Peters P J , Clevers H (2009). Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche. Nature, 459(7244): 262–265
|
44 |
Saxena K, Blutt S E, Ettayebi K, Zeng X L , Broughman J R , Crawford S E , Karandikar U C , Sastri N P , Conner M E , Opekun A R , Graham D Y , Qureshi W , Sherman V , Foulke-Abel J , In J, Kovbasnjuk O, Zachos N C , Donowitz M , Estes M K (2015). Human intestinal enteroids: a new model to study human rotavirus infection, host restriction, and pathophysiology. J Virol, 90(1): 43–56
|
45 |
Schlaermann P, Toelle B, Berger H , Schmidt S C , Glanemann M , Ordemann J , Bartfeld S , Mollenkopf H J , Meyer T F (2016). A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro. Gut, 65(2): 202–213
|
46 |
Schumacher M A , Feng R, Aihara E, Engevik A C , Montrose M H , Ottemann K M , Zavros Y (2015). Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFkB pathway activation: the use of a novel in vitro model to study epithelial response to infection. Helicobacter, 20(1): 19–28
|
47 |
Schwank G, Koo B K, Sasselli V, Dekkers J F , Heo I, Demircan T, Sasaki N , Boymans S , Cuppen E , van der Ent C K , Nieuwenhuis E E , Beekman J M , Clevers H (2013). Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell, 13(6): 653–658
|
48 |
Schwartz R E, Trehan K, Andrus L , Sheahan T P , Ploss A , Duncan S A , Rice C M , Bhatia S N (2012). Modeling hepatitis C virus infection using human induced pluripotent stem cells. Proc Natl Acad Sci USA, 109(7): 2544–2548
|
49 |
Shlomai A, Schwartz R E, Ramanan V, Bhatta A , de Jong Y P , Bhatia S N , Rice C M (2014). Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems. Proc Natl Acad Sci USA, 111(33): 12193–12198
|
50 |
Sigal M, Rothenberg M E, Logan C Y, Lee J Y, Honaker R W, Cooper R L, Passarelli B, Camorlinga M , Bouley D M , Alvarez G , Nusse R , Torres J , Amieva M R (2015). Helicobacter pylori activates and expands Lgr5(+) stem cells through direct colonization of the gastric glands. Gastroenterology, 148(7): 1392–404.e21
|
51 |
Spence J R, Mayhew C N, Rankin S A, Kuhar M F, Vallance J E, Tolle K, Hoskins E E , Kalinichenko V V , Wells S I , Zorn A M , Shroyer N F , Wells J M (2011). Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature, 470(7332): 105–109
|
52 |
Unsworth B R, Lelkes P I (1998). Growing tissues in microgravity. Nat Med, 4(8): 901–907
|
53 |
VanDussen K L , Marinshaw J M , Shaikh N , Miyoshi H , Moon C, Tarr P I, Ciorba M A, Stappenbeck T S (2015). Development of an enhanced human gastrointestinal epithelial culture system to facilitate patient-based assays. Gut, 64(6): 911–920
|
54 |
Wang X, Yamamoto Y, Wilson L H , Zhang T , Howitt B E , Farrow M A , Kern F, Ning G, Hong Y , Khor C C , Chevalier B , Bertrand D , Wu L, Nagarajan N, Sylvester F A , Hyams J S , Devers T , Bronson R , Lacy D B , Ho K Y , Crum C P , McKeon F , Xian W (2015). Cloning and variation of ground state intestinal stem cells. Nature, 522(7555): 173–178
|
55 |
Wilson S S, Tocchi A, Holly M K , Parks W C , Smith J G (2015). A small intestinal organoid model of non-invasive enteric pathogen-epithelial cell interactions. Mucosal Immunol, 8(2): 352–361
|
56 |
Wroblewski L E , Peek R M Jr, Wilson K T (2010). Helicobacter pylori and gastric cancer: factors that modulate disease risk. Clin Microbiol Rev, 23(4): 713–739
|
57 |
Wu X, Robotham J M, Lee E, Dalton S , Kneteman N M , Gilbert D M , Tang H (2012). Productive hepatitis C virus infection of stem cell-derived hepatocytes reveals a critical transition to viral permissiveness during differentiation. PLoS Pathog, 8(4): e1002617
|
58 |
Yin Y, Bijvelds M, Dang W , Xu L, van der Eijk A A, Knipping K, Tuysuz N , Dekkers J F , Wang Y, de Jonge J, Sprengers D , van der Laan L J , Beekman J M , Ten Berge D , Metselaar H J , de Jonge H , Koopmans M P , Peppelenbosch M P , Pan Q (2015). Modeling rotavirus infection and antiviral therapy using primary intestinal organoids. Antiviral Res, 123: 120–131
|
59 |
Yoshida T, Takayama K, Kondoh M , Sakurai F , Tani H, Sakamoto N, Matsuura Y , Mizuguchi H , Yagi K (2011). Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection. Biochem Biophys Res Commun, 416(1-2): 119–124
|
60 |
Yui S, Nakamura T, Sato T , Nemoto Y , Mizutani T , Zheng X , Ichinose S , Nagaishi T , Okamoto R , Tsuchiya K , Clevers H , Watanabe M (2012). Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5+ stem cell. Nat Med, 18(4): 618–623
|
61 |
Zhang Y G, Wu S, Xia Y , Sun J (2014). Salmonella-infected crypt-derived intestinal organoid culture system for host-bacterial interactions. Physiol Rep, 2(9): e12147
|
/
〈 | 〉 |