Current Pathobiology Reports

, Volume 4, Issue 1, pp 1–9 | Cite as

Organoids as Model Systems for Gastrointestinal Diseases: Tissue Engineering Meets Genetic Engineering

Organoid Cultures (Merixtell Huch, Section Editor)
Part of the following topical collections:
  1. Organoid Cultures


Organoids are three-dimensional culture systems that resemble their organ of origin, are genetically stable, and can phenocopy diseases. They enable modeling of various cancer entities such as gastric or colorectal cancer, in addition to other gastrointestinal tract diseases such as inflammatory bowel disease. Genetic engineering tools like CRISPR/Cas9 allow their manipulation to repair mutations or unravel gene functions. Individual patient-derived organoids allow to test therapies in vitro before their in vivo application, bringing personalized medicine to a next level. Organoid biobanks can be used to conduct drug screenings and validate biomarkers. Interactions with microbiota can be investigated in realistic in vitro models. Transplantability of genetically engineered organoids opens up new avenues in the tissue engineering research field. Organoid cultures thus represent a versatile system to model diseases and test therapeutic interventions.


Stem cells Organoids Disease modeling Personalized medicine 



The Stange lab is funded by the European Research Council (#1570398.99), Deutsche Krebshilfe (#111350), Wilhelm-Sander-Stiftung (#2014.104.1), and H.W. & J. Hector Stiftung (M 65.2). Figure 1 was designed with the help of


Recently published papers of particular interest have been highlighted as: • Of importance

  1. 1.
    • Lancaster MA, Knoblich JA (2014) Organogenesis in a dish: modeling development and disease using organoid technologies. Science 345(6194):1247125. Excellent review about differentiation of PSCs and AdSCs into various organoid culture systems Google Scholar
  2. 2.
    Huch M, Koo BK (2015) Modeling mouse and human development using organoid cultures. Development 142(18):3113–3125CrossRefPubMedGoogle Scholar
  3. 3.
    Lancaster MA, Renner M, Martin CA et al (2013) Cerebral organoids model human brain development and microcephaly. Nature 501(7467):373–379CrossRefPubMedGoogle Scholar
  4. 4.
    Muguruma K, Nishiyama A, Kawakami H et al (2015) Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep 10(4):537–550CrossRefPubMedGoogle Scholar
  5. 5.
    Koehler KR, Mikosz AM, Molosh AI et al (2013) Generation of inner ear sensory epithelia from pluripotent stem cells in 3D culture. Nature 500(7461):217–221CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Lee GY, Kenny PA, Lee EH et al (2007) Three-dimensional culture models of normal and malignant breast epithelial cells. Nat Methods 4(4):359–365CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Dontu G, Abdallah WM, Foley JM et al (2003) In vitro propagation and transcriptional profiling of human mammary stem/progenitor cells. Genes Dev 17(10):1253–1270CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Suga H, Kadoshima T, Minaguchi M et al (2011) Self-formation of functional adenohypophysis in three-dimensional culture. Nature 480(7375):57–62CrossRefPubMedGoogle Scholar
  9. 9.
    Eiraku M, Takata N, Ishibashi H et al (2011) Self-organizing optic-cup morphogenesis in three-dimensional culture. Nature 472(7341):51–56CrossRefPubMedGoogle Scholar
  10. 10.
    Nakano T, Ando S, Takata N et al (2012) Self-formation of optic cups and storable stratified neural retina from human ESCs. Cell Stem Cell 10(6):771–785CrossRefPubMedGoogle Scholar
  11. 11.
    Kuwahara A, Ozone C, Nakano T et al (2015) Generation of a ciliary margin-like stem cell niche from self-organizing human retinal tissue. Nat Commun 6:6286CrossRefPubMedGoogle Scholar
  12. 12.
    Hisha H, Tanaka T, Kanno S et al (2013) Establishment of a novel lingual organoid culture system: generation of organoids having mature keratinized epithelium from adult epithelial stem cells. Sci Rep 3:3224CrossRefPubMedPubMedCentralGoogle Scholar
  13. 13.
    Stevens KR, Pabon L, Muskheli V et al (2009) Scaffold-free human cardiac tissue patch created from embryonic stem cells. Tissue Eng Part A 15(6):1211–1222CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Takasato M, Er PX, Becroft M et al (2014) Directing human embryonic stem cell differentiation towards a renal lineage generates a self-organizing kidney. Nat Cell Biol 16(1):118–126CrossRefPubMedGoogle Scholar
  15. 15.
    Batchelder CA, Martinez ML, Duru N et al (2015) Three dimensional culture of human renal cell carcinoma organoids. PLoS One 10(8):e0136758CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kwong J, Chan FL, Wong KK et al (2009) Inflammatory cytokine tumor necrosis factor alpha confers precancerous phenotype in an organoid model of normal human ovarian surface epithelial cells. Neoplasia 11(6):529–541CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    van der Schaft DWJ, van Spreeuwel ACC, Boonen KJM et al (2013) Engineering skeletal muscle tissues from murine myoblast progenitor cells and application of electrical stimulation. JoVE 73:4267Google Scholar
  18. 18.
    Spence JR, Mayhew CN, Rankin SA et al (2011) Directed differentiation of human pluripotent stem cells into intestinal tissue in vitro. Nature 470(7332):105–109CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    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):262–265CrossRefPubMedGoogle Scholar
  20. 20.
    Ootani A, Li X, Sangiorgi E et al (2009) Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche. Nat Med 15(6):701–706CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    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):1762–1772CrossRefPubMedGoogle Scholar
  22. 22.
    • Li X, Nadauld L, Ootani A et al (2014) Oncogenic transformation of diverse gastrointestinal tissues in primary organoid culture. Nat Med 20(7):769–777. Special air-liquid interface methodology for the culturing of complex gastric, pancreatic and intestinal organoids without growth factors and various mutation studies for validation of tumorigenicity in vitro and in vivo Google Scholar
  23. 23.
    • van de Wetering M, Francies HE, Francis JM et al (2015) Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell 161(4):933–945. Establishment of an extensiveLiving biobankwith CRC patient-derived organoids applied for DNA sequencing, transcriptome analysis and personalized drug screening Google Scholar
  24. 24.
    Takebe T, Sekine K, Enomura M et al (2013) Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature 499(7459):481–484CrossRefPubMedGoogle Scholar
  25. 25.
    Huch M, Dorrell C, Boj SF et al (2013) In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494(7436):247–250CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Huch M, Gehart H, van Boxtel R et al (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160(1–2):299–312CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Dye BR, Hill DR, Ferguson MA et al (2015) In vitro generation of human pluripotent stem cell derived lung organoids. Elife. doi: 10.7554/eLife.05098 Google Scholar
  28. 28.
    Lee JH, Bhang DH, Beede A et al (2014) Lung stem cell differentiation in mice directed by endothelial cells via a BMP4-NFATc1-thrombospondin-1 axis. Cell 156(3):440–455CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Greggio C, De Franceschi F, Figueiredo-Larsen M et al (2013) Artificial three-dimensional niches deconstruct pancreas development in vitro. Development 140(21):4452–4462CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Huch M, Bonfanti P, Boj SF et al (2013) Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J 32(20):2708–2721CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Boj SF, Hwang CI, Baker LA et al (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160(1–2):324–338CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Xin L, Lukacs RU, Lawson DA et al (2007) Self-renewal and multilineage differentiation in vitro from murine prostate stem cells. Stem Cells 25(11):2760–2769CrossRefPubMedGoogle Scholar
  33. 33.
    Karthaus WR, Iaquinta PJ, Drost J et al (2014) Identification of multipotent luminal progenitor cells in human prostate organoid cultures. Cell 159(1):163–175CrossRefPubMedGoogle Scholar
  34. 34.
    Gao D, Vela I, Sboner A et al (2014) Organoid cultures derived from patients with advanced prostate cancer. Cell 159(1):176–187CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    McCracken KW, Cata EM, Crawford CM et al (2014) Modelling human development and disease in pluripotent stem-cell-derived gastric organoids. Nature 516(7531):400–404CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Barker N, Huch M, Kujala P et al (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6(1):25–36CrossRefPubMedGoogle Scholar
  37. 37.
    Stange DE, Koo BK, Huch M et al (2013) Differentiated Troy+ chief cells act as reserve stem cells to generate all lineages of the stomach epithelium. Cell 155(2):357–368CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Bartfeld S, Bayram T, van de Wetering M et al (2015) In vitro expansion of human gastric epithelial stem cells and their responses to bacterial infection. Gastroenterology 148(1):126–136, e126Google Scholar
  39. 39.
    Antonica F, Kasprzyk DF, Opitz R et al (2012) Generation of functional thyroid from embryonic stem cells. Nature 491(7422):66–71CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Koo BK, Clevers H (2014) Stem cells marked by the R-spondin receptor Lgr5. Gastroenterology 147(2):289–302CrossRefPubMedGoogle Scholar
  41. 41.
    Andersson-Rolf A, Fink J, Mustata RC et al (2014) A video protocol of retroviral infection in primary intestinal organoid culture. J Vis Exp 90:e51765PubMedGoogle Scholar
  42. 42.
    Drost J, van Jaarsveld RH, Ponsioen B et al (2015) Sequential cancer mutations in cultured human intestinal stem cells. Nature 521(7550):43–47CrossRefPubMedGoogle Scholar
  43. 43.
    Koo BK, Stange DE, Sato T et al (2012) Controlled gene expression in primary Lgr5 organoid cultures. Nat Methods 9(1):81–83CrossRefGoogle Scholar
  44. 44.
    • Matano M, Date S, Shimokawa M et al (2015) Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med 21(3):256–262. Modeling of the most common CRC mutations via CRISPR/Cas9 genome editing, establishment of a media-based selection method and validation of the tumorigenicity in vitro and in vivo Google Scholar
  45. 45.
    Schwank G, Andersson-Rolf A, Koo BK et al (2013) Generation of BAC transgenic epithelial organoids. PLoS One 8(10):e76871CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    • Schwank G, Koo BK, Sasselli V et al (2013) Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell 13(6):653–658. Repair of a disease-causing mutation by homologous recombination with CRISPR/Cas9 Google Scholar
  47. 47.
    • Yui S, Nakamura T, Sato T et al (2012) Functional engraftment of colon epithelium expanded in vitro from a single adult Lgr5(+) stem cell. Nat Med 18(4):618–623. First study showing the transplantability of organoid cultures for the repair of damaged tissue Google Scholar
  48. 48.
    Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65(2):87–108CrossRefPubMedGoogle Scholar
  49. 49.
    Cancer Genome Atlas N (2012) Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407):330–337CrossRefGoogle Scholar
  50. 50.
    Sachs N, Clevers H (2014) Organoid cultures for the analysis of cancer phenotypes. Curr Opin Genet Dev 24:68–73CrossRefPubMedGoogle Scholar
  51. 51.
    Barker N, van Es JH, Kuipers J et al (2007) Identification of stem cells in small intestine and colon by marker gene Lgr5. Nature 449(7165):1003–1007CrossRefPubMedGoogle Scholar
  52. 52.
    Munoz J, Stange DE, Schepers AG et al (2012) The Lgr5 intestinal stem cell signature: robust expression of proposed quiescent ‘+4’ cell markers. EMBO J 31(14):3079–3091CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Radtke F, Clevers H (2005) Self-renewal and cancer of the gut: two sides of a coin. Science 307(5717):1904–1909CrossRefPubMedGoogle Scholar
  54. 54.
    Chen EC, Karl TA, Kalisky T et al (2015) KIT signaling promotes growth of colon xenograft tumors in mice and is up-regulated in a subset of human colon cancers. Gastroenterology 149(3):705–717, e702Google Scholar
  55. 55.
    Calon A, Lonardo E, Berenguer-Llergo A et al (2015) Stromal gene expression defines poor-prognosis subtypes in colorectal cancer. Nat Genet 47(4):320–329CrossRefPubMedGoogle Scholar
  56. 56.
    Wiener Z, Band AM, Kallio P et al (2014) Oncogenic mutations in intestinal adenomas regulate Bim-mediated apoptosis induced by TGF-beta. Proc Natl Acad Sci USA 111(21):E2229–E2236CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Yamauchi M, Otsuka K, Kondo H et al (2014) A novel in vitro survival assay of small intestinal stem cells after exposure to ionizing radiation. J Radiat Res 55(2):381–390CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Tomono A, Yamashita K, Kanemitsu K et al (2015) Prognostic significance of pathological response to preoperative chemoradiotherapy in patients with locally advanced rectal cancer. Int J Clin Oncol. doi: 10.1007/s10147-015-0900-x PubMedGoogle Scholar
  59. 59.
    Vassilev LT, Vu BT, Graves B et al (2004) In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303(5659):844–848CrossRefPubMedGoogle Scholar
  60. 60.
    Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140(6):883–899CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Oshima H, Nakayama M, Han TS et al (2015) Suppressing TGFbeta signaling in regenerating epithelia in an inflammatory microenvironment is sufficient to cause invasive intestinal cancer. Cancer Res 75(4):766–776CrossRefPubMedGoogle Scholar
  62. 62.
    Koo BK, Spit M, Jordens I et al (2012) Tumour suppressor RNF43 is a stem-cell E3 ligase that induces endocytosis of Wnt receptors. Nature 488(7413):665–669CrossRefPubMedGoogle Scholar
  63. 63.
    Wong VW, Stange DE, Page ME et al (2012) Lrig1 controls intestinal stem-cell homeostasis by negative regulation of ErbB signalling. Nat Cell Biol 14(4):401–408CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    van der Flier LG, van Gijn ME, Hatzis P et al (2009) Transcription factor achaete scute-like 2 controls intestinal stem cell fate. Cell 136(5):903–912CrossRefPubMedGoogle Scholar
  65. 65.
    Schuijers J, van der Flier LG, van Es J et al (2014) Robust cre-mediated recombination in small intestinal stem cells utilizing the olfm4 locus. Stem Cell Reports 3(2):234–241CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Huch M (2015) Building stomach in a dish. Nat Cell Biol 17(8):966–967CrossRefPubMedGoogle Scholar
  67. 67.
    Noguchi TA, Ninomiya N, Sekine M et al (2015) Generation of stomach tissue from mouse embryonic stem cells. Nat Cell Biol 17(8):984–993CrossRefPubMedGoogle Scholar
  68. 68.
    Nadauld LD, Garcia S, Natsoulis G et al (2014) Metastatic tumor evolution and organoid modeling implicate TGFBR2 as a cancer driver in diffuse gastric cancer. Genome Biol 15(8):428CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Salama NR, Hartung ML, Muller A (2013) Life in the human stomach: persistence strategies of the bacterial pathogen Helicobacter pylori. Nat Rev Microbiol 11(6):385–399CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Schlaermann P, Toelle B, Berger H et al (2014) A novel human gastric primary cell culture system for modelling Helicobacter pylori infection in vitro. Gut 65(2):202–213CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Schumacher MA, Feng R, Aihara E et al (2015) Helicobacter pylori-induced Sonic Hedgehog expression is regulated by NFkappaB pathway activation: the use of a novel in vitro model to study epithelial response to infection. Helicobacter 20(1):19–28CrossRefPubMedGoogle Scholar
  72. 72.
    Sigal M, Rothenberg ME, Logan CY et al (2015) Helicobacter pylori activates and expands Lgr5(+) stem cells through direct colonization of the gastric glands. Gastroenterology 148(7):1392–1404, e1321Google Scholar
  73. 73.
    Marchesi JR, Adams DH, Fava F et al (2015) The gut microbiota and host health: a new clinical frontier. Gut 65(2):330–339CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Lukovac S, Belzer C, Pellis L et al (2014) Differential modulation by Akkermansia muciniphila and Faecalibacterium prausnitzii of host peripheral lipid metabolism and histone acetylation in mouse gut organoids. MBio. doi: 10.1128/mBio.01438-14 PubMedPubMedCentralGoogle Scholar
  75. 75.
    Finkbeiner SR, Zeng XL, Utama B et al (2012) Stem cell-derived human intestinal organoids as an infection model for rotaviruses. MBio 3(4):e00159–00112CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Yin Y, Bijvelds M, Dang W et al (2015) Modeling rotavirus infection and antiviral therapy using primary intestinal organoids. Antiviral Res 65(2):330–339Google Scholar
  77. 77.
    Zhang YG, Wu S, Xia Y et al (2014) Salmonella-infected crypt-derived intestinal organoid culture system for host-bacterial interactions. Physiol Rep. doi: 10.14814/phy2.12147 Google Scholar
  78. 78.
    Engevik MA, Aihara E, Montrose MH et al (2013) Loss of NHE3 alters gut microbiota composition and influences Bacteroides thetaiotaomicron growth. Am J Physiol Gastrointest Liver Physiol 305(10):G697–711CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Engevik MA, Engevik KA, Yacyshyn MB et al (2015) Human Clostridium difficile infection: inhibition of NHE3 and microbiota profile. Am J Physiol Gastrointest Liver Physiol 308(6):G497–509CrossRefPubMedGoogle Scholar
  80. 80.
    Engevik MA, Yacyshyn MB, Engevik KA et al (2015) Human Clostridium difficile infection: altered mucus production and composition. Am J Physiol Gastrointest Liver Physiol 308(6):G510–524CrossRefPubMedGoogle Scholar
  81. 81.
    Leslie JL, Huang S, Opp JS et al (2015) Persistence and toxin production by Clostridium difficile within human intestinal organoids result in disruption of epithelial paracellular barrier function. Infect Immun 83(1):138–145CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Wilson SS, Tocchi A, Holly MK et al (2015) A small intestinal organoid model of non-invasive enteric pathogen-epithelial cell interactions. Mucosal Immunol 8(2):352–361CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Viswanathan VK (2014) Muramyl dipeptide: not just another brick in the wall. Gut Microbes 5(3):275–276CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Nigro G, Rossi R, Commere PH et al (2014) The cytosolic bacterial peptidoglycan sensor Nod2 affords stem cell protection and links microbes to gut epithelial regeneration. Cell Host Microbe 15(6):792–798CrossRefPubMedGoogle Scholar
  85. 85.
    Pham TA, Clare S, Goulding D et al (2014) Epithelial IL-22RA1-mediated fucosylation promotes intestinal colonization resistance to an opportunistic pathogen. Cell Host Microbe 16(4):504–516CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Li Y, Teo WL, Low MJ et al (2014) Constitutive TLR4 signalling in intestinal epithelium reduces tumor load by increasing apoptosis in APC(Min/+) mice. Oncogene 33(3):369–377CrossRefPubMedGoogle Scholar
  87. 87.
    Rodansky ES, Johnson LA, Huang S et al (2015) Intestinal organoids: a model of intestinal fibrosis for evaluating anti-fibrotic drugs. Exp Mol Pathol 98(3):346–351CrossRefPubMedGoogle Scholar
  88. 88.
    Schumacher MA, Aihara E, Feng R et al (2015) The use of murine-derived fundic organoids in studies of gastric physiology. J Physiol 593(8):1809–1827CrossRefPubMedGoogle Scholar
  89. 89.
    Mokry M, Middendorp S, Wiegerinck CL et al (2014) Many inflammatory bowel disease risk loci include regions that regulate gene expression in immune cells and the intestinal epithelium. Gastroenterology 146(4):1040–1047CrossRefPubMedGoogle Scholar
  90. 90.
    Dammann K, Khare V, Lang M et al (2015) PAK1 modulates a PPARgamma/NF-kappaB cascade in intestinal inflammation. Biochim Biophys Acta 1853(10 Pt A):2349–2360CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Fordham RP, Yui S, Hannan NR et al (2013) Transplantation of expanded fetal intestinal progenitors contributes to colon regeneration after injury. Cell Stem Cell 13(6):734–744CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Fukuda M, Mizutani T, Mochizuki W et al (2014) Small intestinal stem cell identity is maintained with functional Paneth cells in heterotopically grafted epithelium onto the colon. Genes Dev 28(16):1752–1757CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Bigorgne AE, Farin HF, Lemoine R et al (2014) TTC7A mutations disrupt intestinal epithelial apicobasal polarity. J Clin Invest 124(1):328–337CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Zomer-van Ommen DD, Vijftigschild LA, Kruisselbrink E et al (2015) Limited premature termination codon suppression by read-through agents in cystic fibrosis intestinal organoids. J Cyst FibrosGoogle Scholar
  95. 95.
    Trzcinska-Daneluti AM, Chen A, Nguyen L et al (2015) RNA interference screen to identify kinases that suppress rescue of DeltaF508-CFTR. Mol Cell Proteomics 14(6):1569–1583CrossRefPubMedGoogle Scholar
  96. 96.
    Okiyoneda T, Veit G, Dekkers JF et al (2013) Mechanism-based corrector combination restores DeltaF508-CFTR folding and function. Nat Chem Biol 9(7):444–454CrossRefPubMedGoogle Scholar
  97. 97.
    Dekkers JF, van der Ent CK, Beekman JM (2013) Novel opportunities for CFTR-targeting drug development using organoids. Rare Dis 1:e27112CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Dekkers JF, Wiegerinck CL, de Jonge HR et al (2013) A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med 19(7):939–945CrossRefPubMedGoogle Scholar
  99. 99.
    Mou H, Brazauskas K, Rajagopal J (2015) Personalized medicine for cystic fibrosis: establishing human model systems. Pediatr Pulmonol 50(Suppl 40):S14–23CrossRefPubMedGoogle Scholar
  100. 100.
    Ikpa PT, Bijvelds MJ, de Jonge HR (2014) Cystic fibrosis: toward personalized therapies. Int J Biochem Cell Biol 52:192–200CrossRefPubMedGoogle Scholar
  101. 101.
    Brugmann SA, Wells JM (2013) Building additional complexity to in vitro-derived intestinal tissues. Stem Cell Res Ther 4(Suppl 1):S1CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Grant CN, Grikscheit TC (2013) Tissue engineering: a promising therapeutic approach to necrotizing enterocolitis. Semin Pediatr Surg 22(2):112–116CrossRefPubMedGoogle Scholar
  103. 103.
    Belchior GG, Sogayar MC, Grikscheit TC (2014) Stem cells and biopharmaceuticals: vital roles in the growth of tissue-engineered small intestine. Semin Pediatr Surg 23(3):141–149CrossRefPubMedGoogle Scholar
  104. 104.
    Behjati S, Huch M, van Boxtel R et al (2014) Genome sequencing of normal cells reveals developmental lineages and mutational processes. Nature 513(7518):422–425CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Kristin Werner
    • 1
  • Jürgen Weitz
    • 1
  • Daniel E. Stange
    • 1
  1. 1.Department of Gastrointestinal, Thoracic and Vascular SurgeryUniversity Hospital Carl Gustav Carus, Technische Universität DresdenDresdenGermany

Personalised recommendations