Organoid As a Novel Technology for Disease Modeling

Abstract

The organoid technology is capable to create more real-like in vitro models in terms of structure and function of the origin of the tissue. Since the three-dimensional model is able to illustrate disease pathology, cell differentiation, and recapitulation of self-renewal, lead organoid technology as a promising disease model to fill the gap between conventional two-dimensional, and in vivo disease models. The review describes the recent development of organoid disease modeling approaches.

Keywords

• Organoid
• Disease modeling
• Stem cell

References

1. 1. Duval K, Grover H, Han LH, Mou Y, Pegoraro AF, Fredberg J, et al. Modeling physiological events in 2D vs. 3D cell culture. Physiology. 2017.
2. 2. Byrne AT, Alférez DG, Amant F, Annibali D, Arribas J, Biankin A V., et al. Interrogating open issues in cancer precision medicine with patient-derived xenografts. Nature Reviews Cancer. 2017.
3. 3. Haycock JW. 3D cell culture: a review of current approaches and techniques. Methods in molecular biology (Clifton, N.J.). 2011.
4. 4. Mahe MM, Aihara E, Schumacher MA, Zavros Y, Montrose MH, Helmrath MA, et al. Establishment of Gastrointestinal Epithelial Organoids. Curr Protoc Mouse Biol. 2013;
5. 5. Takebe T, Sekine K, Enomura M, Koike H, Kimura M, Ogaeri T, et al. Vascularized and functional human liver from an iPSC-derived organ bud transplant. Nature. 2013;
6. 6. Schreurs RRCE, Baumdick ME, Sagebiel AF, Kaufmann M, Mokry M, Klarenbeek PL, et al. Human Fetal TNF-α-Cytokine-Producing CD4 + Effector Memory T Cells Promote Intestinal Development and Mediate Inflammation Early in Life. Immunity. 2019;
7. 7. Noel G, Baetz NW, Staab JF, Donowitz M, Kovbasnjuk O, Pasetti MF, et al. A primary human macrophage-enteroid co-culture model to investigate mucosal gut physiology and host-pathogen interactions. Sci Rep. 2017;
8. 8. Koike H, Iwasawa K, Ouchi R, Maezawa M, Giesbrecht K, Saiki N, et al. Modelling human hepato-biliary-pancreatic organogenesis from the foregut–midgut boundary. Nature. 2019;

9. 9. Fujii M, Matano M, Nanki K, Sato T. Efficient genetic engineering of human intestinal organoids using electroporation. Nat Protoc. 2015.
10. 10. Dutta D, Heo I, Clevers H. Disease Modeling in Stem Cell-Derived 3D Organoid Systems. Trends in Molecular Medicine. 2017.
11. 11. Liu B, Song Y, Liu D. Recent development in clinical applications of PD-1 and PD-L1 antibodies for cancer immunotherapy. Journal of Hematology and Oncology. 2017.
12. 12. Pang Y, Hou X, Yang C, Liu Y, Jiang G. Advances on chimeric antigen receptor-modified T-cell therapy for oncotherapy. Molecular Cancer. 2018. 13. Zhou J, Su J, Fu X, Zheng L, Yin Z. Microfluidic device for primary tumor spheroid isolation. Exp Hematol Oncol. 2017.
13. 14. Ben-David U, Ha G, Tseng YY, Greenwald NF, Oh C, Shih J, et al. Patient-derived xenografts undergo mouse-specific tumor evolution. Nat Genet. 2017.
14. 15. Na JC, Kim JH, Kim SY, Gu YR, Jun DY, Lee HH, et al. Establishment of patient-derived three-dimensional organoid culture in renal cell carcinoma. Investig Clin Urol. 2020; 16. Van De Wetering M, Francies HE, Francis JM, Bounova G, Iorio F, Pronk A, et al. Prospective derivation of a living organoid biobank of colorectal cancer patients. Cell. 2015.
15. 17. Weeber F, Van De Wetering M, Hoogstraat M, Dijkstra KK, Krijgsman O, Kuilman T, et al. Preserved genetic diversity in organoids cultured from biopsies of human colorectal cancer metastases. Proc Natl Acad Sci U S A. 2015.
16. 18. Gao D, Vela I, Sboner A, Iaquinta PJ, Karthaus WR, Gopalan A, et al. Organoid cultures derived from patients with advanced prostate cancer. Cell. 2014.
17. 19. Hill SJ, Decker B, Roberts EA, Horowitz NS, Muto MG, Worley MJ, et al. Prediction of DNA repair inhibitor response in short-term patient-derived ovarian cancer organoids. Cancer Discov. 2018.
18. 20. Fujii M, Shimokawa M, Date S, Takano A, Matano M, Nanki K, et al. A Colorectal Tumor Organoid Library Demonstrates Progressive Loss of Niche Factor Requirements during Tumorigenesis. Cell Stem Cell. 2016.
19. 21. Yeung TM, Gandhi SC, Wilding JL, Muschel R, Bodmer WF. Cancer stem cells from colorectal cancer-derived cell lines. Proc Natl Acad Sci U S A. 2010; 22. Onuma K, Ochiai M, Orihashi K, Takahashi M, Imai T, Nakagama H, et al. Genetic reconstitution of tumorigenesis in primary intestinal cells. Proc Natl Acad Sci U S A. 2013.
20. 23. Matano M, Date S, Shimokawa M, Takano A, Fujii M, Ohta Y, et al. Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids. Nat Med. 2015.
21. 24. Scanu T, Spaapen RM, Bakker JM, Pratap CB, Wu L en, Hofland I, et al. Salmonella Manipulation of Host Signaling Pathways Provokes Cellular Transformation Associated with Gallbladder Carcinoma. Cell Host Microbe. 2015.
22. 25. Davies H, Glodzik D, Morganella S, Yates LR, Staaf J, Zou X, et al. HRDetect is a predictor of BRCA1 and BRCA2 deficiency based on mutational signatures. Nat Med. 2017; 26. Driehuis E, Kretzschmar K, Clevers H. Establishment of patient-derived cancer organoids for drug-screening applications. Nat Protoc. 2020.
23. 27. Vlachogiannis G, Hedayat S, Vatsiou A, Jamin Y, Fernández-Mateos J, Khan K, et al. Patient-derived organoids model treatment response of metastatic gastrointestinal cancers. Science (80- ). 2018.
24. 28. Ganesh K, Wu C, O’Rourke KP, Szeglin BC, Zheng Y, Sauvé CEG, et al. A rectal cancer organoid platform to study individual responses to chemoradiation. Nat Med. 2019.
25. 29. Yoshida GJ. Applications of patient-derived tumor xenograft models and tumor organoids. Journal of Hematology and Oncology. 2020.
26. 30. Benson CA, Powell HR, Liput M, Dinham S, Freedman DA, Ignatowski TA, et al. Immune Factor, TNFα, Disrupts Human Brain Organoid Development Similar to Schizophrenia—Schizophrenia Increases Developmental Vulnerability to TNFα. Front Cell Neurosci. 2020.
27. 31. Daviaud N, Chevalier C, Friedel RH, Zou H. Distinct Vulnerability and Resilience of Human Neuroprogenitor Subtypes in Cerebral Organoid Model of Prenatal Hypoxic Injury. Front Cell Neurosci. 2019.
28. 32. Simmnacher K, Lanfer J, Rizo T, Kaindl J, Winner B. Modeling Cell-Cell Interactions in Parkinson’s Disease Using Human Stem Cell-Based Models. Frontiers in Cellular Neuroscience. 2020.
29. 33. Chen A, Guo Z, Fang L, Bian S. Application of Fused Organoid Models to Study Human Brain Development and Neural Disorders. Frontiers in Cellular Neuroscience. 2020.
30. 34. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex genome engineering using CRISPR/Cas systems. Science (80- ). 2013.
31. 35. Zou X, Owusu M, Harris R, Jackson SP, Loizou JI, Nik-Zainal S. Validating the concept of mutational signatures with isogenic cell models. Nat Commun. 2018.
32. 36. Perez-Lanzon M, Kroemer G, Maiuri MC. Organoids for Modeling Genetic Diseases. In: International Review of Cell and Molecular Biology. 2018.
33. 37. De Boeck K, Vermeulen F, Dupont L. The diagnosis of cystic fibrosis. Presse Medicale. 2017.
34. 38. Schwank G, Koo BK, Sasselli V, Dekkers JF, Heo I, Demircan T, et al. Functional repair of CFTR by CRISPR/Cas9 in intestinal stem cell organoids of cystic fibrosis patients. Cell Stem Cell. 2013.
35. 39. Artegiani B, Clevers H. Use and application of 3D-organoid technology. Human molecular genetics. 2018.
36. 40. Jo J, Xiao Y, Sun AX, Cukuroglu E, Tran HD, Göke J, et al. Midbrain-like Organoids from Human Pluripotent Stem Cells Contain Functional Dopaminergic and Neuromelanin-Producing Neurons. Cell Stem Cell. 2016.
37. 41. Pasca AM, Sloan SA, Clarke LE, Tian Y, Makinson CD, Huber N, et al. Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nat Methods. 2015.
38. 42. Hossein F. An overview of the current medical literature on Zika virus. Biophysical Reviews. 2020. 43. Qian X, Nguyen HN, Jacob F, Song H, Ming GL. Using brain organoids to understand Zika virus-induced microcephaly. Dev. 2017.
39. 44. Xu M, Lee EM, Wen Z, Cheng Y, Huang WK, Qian X, et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016.
40. 45. Zhou T, Tan L, Cederquist GY, Fan Y, Hartley BJ, Mukherjee S, et al. High-Content Screening in hPSC-Neural Progenitors Identifies Drug Candidates that Inhibit Zika Virus Infection in Fetal-like Organoids and Adult Brain. Cell Stem Cell. 2017.
41. 46. T. M, N. H, J. G, D. H, H. SSSS, J. T, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020.
42. 47. Montalvan V, Lee J, Bueso T, De Toledo J, Rivas K. Neurological manifestations of COVID-19 and other coronavirus infections: A systematic review. Clinical Neurology and Neurosurgery. 2020.
43. 48. Pellegrini L, Albecka A, Mallery DL, Kellner MJ, Paul D, Carter AP, et al. SARS-CoV-2 Infects the Brain Choroid Plexus and Disrupts the Blood-CSF Barrier in Human Brain Organoids. Cell Stem Cell. 2020.
44. 49. Mullenders J, de Jongh E, Brousali A, Roosen M, Blom JPA, Begthel H, et al. Mouse and human urothelial cancer organoids: A tool for bladder cancer research. Proc Natl Acad Sci U S A. 2019.
45. 50. Yao Y, Xu X, Yang L, Zhu J, Wan J, Shen L, et al. Patient-Derived Organoids Predict Chemoradiation Responses of Locally Advanced Rectal Cancer. Cell Stem Cell. 2020.
46. 51. Schnalzger TE, Groot MH, Zhang C, Mosa MH, Michels BE, Röder J, et al. 3D model for CAR ‐mediated cytotoxicity using patient‐derived colorectal cancer organoids . EMBO J. 2019.
47. 52. Drost J, Van Jaarsveld RH, Ponsioen B, Zimberlin C, Van Boxtel R, Buijs A, et al. Sequential cancer mutations in cultured human intestinal stem cells. Nature. 2015.
48. 53. Yang L, Liu B, Chen H, Gao R, Huang K, Guo Q, et al. Progress in the application of organoids to breast cancer research. Journal of Cellular and Molecular Medicine. 2020.
49. 54. Griscelli F, Oudrirhi N, Feraud O, Divers D, Portier L, Turhan AG, et al. Generation of induced pluripotent stem cell (iPSC) line from a patient with triple negative breast cancer with hereditary exon 17 deletion of BRCA1 gene. Stem Cell Res. 2017.
50. 55. Sachs N, de Ligt J, Kopper O, Gogola E, Bounova G, Weeber F, et al. A Living Biobank of Breast Cancer Organoids Captures Disease Heterogeneity. Cell. 2018.
51. 56. Hwang JW, Desterke C, Féraud O, Richard S, Ferlicot S, Verkarre V, et al. IPSC-derived Cancer Organoids Recapitulate Genomic and Phenotypic Alterations of c-met-mutated Hereditary Kidney Cancer. bioRxiv. 2019.
52. 57. Wang S, Gao D, Chen Y. The potential of organoids in urological cancer research. Nature Reviews Urology. 2017.
53. 58. Batchelder CA, Martinez ML, Duru N, Meyers FJ, Tarantal AF. Three dimensional culture of human renal cell carcinoma organoids. PLoS One. 2015.
54. 59. Nanki Y, Chiyoda T, Hirasawa A, Ookubo A, Itoh M, Ueno M, et al. Patient-derived ovarian cancer organoids capture the genomic profiles of primary tumours applicable for drug sensitivity and resistance testing. Sci Rep. 2020.
55. 60. Kopper O, de Witte CJ, Lõhmussaar K, Valle-Inclan JE, Hami N, Kester L, et al. An organoid platform for ovarian cancer captures intra- and interpatient heterogeneity. Nat Med. 2019.
56. 61. Shi R, Radulovich N, Ng C, Liu N, Notsuda H, Cabanero M, et al. Organoid cultures as preclinical models of non-small cell lung cancer. Clin Cancer Res. 2020.
57. 62. Kim M, Mun H, Sung CO, Cho EJ, Jeon HJ, Chun SM, et al. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun. 2019.
58. 63. Dijkstra KK, Cattaneo CM, Weeber F, Chalabi M, van de Haar J, Fanchi LF, et al. Generation of Tumor-Reactive T Cells by Co-culture of Peripheral Blood Lymphocytes and Tumor Organoids. Cell. 2018.
59. 64. Broutier L, Mastrogiovanni G, Verstegen MMA, Francies HE, Gavarró LM, Bradshaw CR, et al. Human primary liver cancer-derived organoid cultures for disease modeling and drug screening. Nat Med. 2017.
60. 65. Bhaduri A, Andrews MG, Mancia Leon W, Jung D, Shin D, Allen D, et al. Cell stress in cortical organoids impairs molecular subtype specification. Nature. 2020.
61. 66. Ballabio C, Anderle M, Gianesello M, Lago C, Miele E, Cardano M, et al. Modeling medulloblastoma in vivo and with human cerebellar organoids. Nat Commun. 2020.
62. 67. Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH, et al. A Patient-Derived Glioblastoma Organoid Model and Biobank Recapitulates Inter- and Intra-tumoral Heterogeneity. Cell. 2020.
63. 68. Beshiri ML, Tice CM, Tran C, Nguyen HM, Sowalsky AG, Agarwal S, et al. A PDX/Organoid biobank of advanced prostate cancers captures genomic and phenotypic heterogeneity for disease modeling and therapeutic screening. Clin Cancer Res. 2018.
64. 69. Dunnack JJ, LoTurco JJ. Of Mice and Men: Species-Specific Organoid Models of Neocortical Malformation. Cell Stem Cell. 2017.
65. 70. Gabriel E, Ramani A, Altinisik N, Gopalakrishnan J. Human Brain Organoids to Decode Mechanisms of Microcephaly. Frontiers in Cellular Neuroscience. 2020.
66. 71. Kelava I, Lancaster MA. Stem Cell Models of Human Brain Development. Cell Stem Cell. 2016.
67. 72. Chan WK, Griffiths R, Price DJ, Mason JO. Cerebral organoids as tools to identify the developmental roots of autism. Molecular Autism. 2020.
68. 73. Hohmann SS, Ilieva M, Michel TM. In vitro models for ASD-patient-derived iPSCs and cerebral organoids. In: Progress in Molecular Biology and Translational Science. 2020.
69. 74. Mariani J, Coppola G, Zhang P, Abyzov A, Provini L, Tomasini L, et al. FOXG1-Dependent Dysregulation of GABA/Glutamate Neuron Differentiation in Autism Spectrum Disorders. Cell. 2015.
70. 75. Papaspyropoulos A, Tsolaki M, Foroglou N, Pantazaki AA. Modeling and Targeting Alzheimer’s Disease With Organoids. Frontiers in Pharmacology. 2020.
71. 76. Kim S, Li J, Mahairaki V. Stem cell-derived three-dimensional (organoid) models of Alzheimer’s disease: a precision medicine approach. Neural Regen Res. 2021.
72. 77. Monzel AS, Smits LM, Hemmer K, Hachi S, Moreno EL, van Wuellen T, et al. Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells. Stem Cell Reports. 2017.
73. 78. Sommer CA, Capilla A, Molina-Estevez FJ, Gianotti-Sommer A, Skvir N, Caballero I, et al. Modeling APC mutagenesis and familial adenomatous polyposis using human iPS cells. PLoS One. 2018.
74. 79. Crespo M, Vilar E, Tsai SY, Chang K, Amin S, Srinivasan T, et al. Colonic organoids derived from human induced pluripotent stem cells for modeling colorectal cancer and drug testing. Nat Med. 2017.
75. 80. Berkers G, van Mourik P, Vonk AM, Kruisselbrink E, Dekkers JF, de Winter-de Groot KM, et al. Rectal Organoids Enable Personalized Treatment of Cystic Fibrosis. Cell Rep. 2019.
76. 81. Dekkers JF, Wiegerinck CL, De Jonge HR, Bronsveld I, Janssens HM, De Winter-De Groot KM, et al. A functional CFTR assay using primary cystic fibrosis intestinal organoids. Nat Med. 2013.
77. 82. Guan Y, Xu D, Garfin PM, Ehmer U, Hurwitz M, Enns G, et al. Human hepatic organoids for the analysis of human genetic diseases. JCI insight. 2017.
78. 83. Freedman BS, Brooks CR, Lam AQ, Fu H, Morizane R, Agrawal V, et al. Modelling kidney disease with CRISPR-mutant kidney organoids derived from human pluripotent epiblast spheroids. Nat Commun. 2015.
79. 84. Bershteyn M, Nowakowski TJ, Pollen AA, Di Lullo E, Nene A, Wynshaw-Boris A, et al. Human iPSC-Derived Cerebral Organoids Model Cellular Features of Lissencephaly and Reveal Prolonged Mitosis of Outer Radial Glia. Cell Stem Cell. 2017.
80. 85. Iefremova V, Manikakis G, Krefft O, Jabali A, Weynans K, Wilkens R, et al. An Organoid-Based Model of Cortical Development Identifies Non-Cell-Autonomous Defects in Wnt Signaling Contributing to Miller-Dieker Syndrome. Cell Rep. 2017.
81. 86. Gomes AR, Fernandes TG, Vaz SH, Silva TP, Bekman EP, Xapelli S, et al. Modeling Rett Syndrome With Human Patient-Specific Forebrain Organoids. Front Cell Dev Biol. 2020.
82. 87. Feldman D, Banerjee A, Sur M. Developmental Dynamics of Rett Syndrome. Neural Plasticity. 2016.
83. 88. Sloan SA, Andersen J, Pașca AM, Birey F, Pașca SP. Generation and assembly of human brain region–specific three-dimensional cultures. Nat Protoc. 2018.
84. 89. Bigorgne AE, Farin HF, Lemoine R, Mahlaoui N, Lambert N, Gil M, et al. TTC7A mutations disrupt intestinal epithelial apicobasal polarity. J Clin Invest. 2014.
85. 90. Watanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh BS, et al. Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection. Cell Rep. 2017.
86. 91. Lamers MM, Beumer J, Vaart J Van Der, Knoops K, Puschhof J, Breugem TI, et al. SARS-CoV-2 productively infects human gut enterocytes. Science (80- ). 2020.
87. 92. Bartfeld S, Clevers H. Organoids as model for infectious diseases: Culture of human and murine stomach organoids and microinjection of helicobacter pylori. J Vis Exp. 2015.