Abstract
Human cerebral organoids are an exciting and novel model system emerging in the field of neurobiology. Cerebral organoids are spheres of self-organizing, neuronal lineage tissue that can be differentiated from human pluripotent stem cells and that present the possibility of on-demand human neuronal cultures that can be used for non-invasively investigating diseases affecting the brain. Compared with existing humanized cell models, they provide a more comprehensive replication of the human cerebral environment. The potential of the human cerebral organoid model is only just beginning to be elucidated, but initial studies have indicated that they could prove to be a valuable model for neurodegenerative diseases such as prion disease. The application of the cerebral organoid model to prion disease, what has been learned so far and the future potential of this model are discussed in this review.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA, Yeromin AV, Scarfone VM, Marsh SE, Fimbres C, Caraway CA, Fote GM, Madany AM, Agrawal A, Kayed R, Gylys KH, Cahalan MD, Cummings BJ, Antel JP, Mortazavi A, Carson MJ, Poon WW, Blurton-Jones M (2017) iPSC-Derived Human Microglia-like Cells to Study Neurological Diseases. Neuron 94(2):278-293.e279. https://doi.org/10.1016/j.neuron.2017.03.042
Adler V, Zeiler B, Kryukov V, Kascsak R, Rubenstein R, Grossman A (2003) Small, highly structured RNAs participate in the conversion of human recombinant PrP(Sen) to PrP(Res) in vitro. J Mol Biol 332(1):47–57. https://doi.org/10.1016/s0022-2836(03)00919-7
Arjona A, Simarro L, Islinger F, Nishida N, Manuelidis L (2004) Two Creutzfeldt-Jakob disease agents reproduce prion protein-independent identities in cell cultures. Proc Natl Acad Sci U S A 101(23):8768–8773. https://doi.org/10.1073/pnas.0400158101
Asante EA, Gowland I, Grimshaw A, Linehan JM, Smidak M, Houghton R, Osiguwa O, Tomlinson A, Joiner S, Brandner S, Wadsworth JDF, Collinge J (2009) Absence of spontaneous disease and comparative prion susceptibility of transgenic mice expressing mutant human prion proteins. J Gen Virol 90(Pt 3):546–558. https://doi.org/10.1099/vir.0.007930-0
Asante EA, Linehan JM, Desbruslais M, Joiner S, Gowland I, Wood AL, Welch J, Hill AF, Lloyd SE, Wadsworth JD, Collinge J (2002) BSE prions propagate as either variant CJD-like or sporadic CJD-like prion strains in transgenic mice expressing human prion protein. EMBO J 21(23):6358–6366. https://doi.org/10.1093/emboj/cdf653
Asante EA, Linehan JM, Gowland I, Joiner S, Fox K, Cooper S, Osiguwa O, Gorry M, Welch J, Houghton R, Desbruslais M, Brandner S, Wadsworth JD, Collinge J (2006) Dissociation of pathological and molecular phenotype of variant Creutzfeldt-Jakob disease in transgenic human prion protein 129 heterozygous mice. Proc Natl Acad Sci U S A 103(28):10759–10764. https://doi.org/10.1073/pnas.0604292103
Asante EA, Smidak M, Grimshaw A, Houghton R, Tomlinson A, Jeelani A, Jakubcova T, Hamdan S, Richard-Londt A, Linehan JM, Brandner S, Alpers M, Whitfield J, Mead S, Wadsworth JD, Collinge J (2015) A naturally occurring variant of the human prion protein completely prevents prion disease. Nature 522(7557):478–481. https://doi.org/10.1038/nature14510
Bagley JA, Reumann D, Bian S, Lévi-Strauss J, Knoblich JA (2017) Fused cerebral organoids model interactions between brain regions. Nat Methods 14(7):743–751. https://doi.org/10.1038/nmeth.4304
Baiardi S, Rossi M, Mammana A, Appleby BS, Barria MA, Calì I, Gambetti P, Gelpi E, Giese A, Ghetti B, Herms J, Ladogana A, Mikol J, Pal S, Ritchie DL, Ruf V, Windl O, Capellari S, Parchi P (2021) Phenotypic diversity of genetic Creutzfeldt-Jakob disease: a histo-molecular-based classification. Acta Neuropathol. https://doi.org/10.1007/s00401-021-02350-y
Baldwin KJ, Correll CM (2019) Prion Disease. Semin Neurol 39(4):428–439. https://doi.org/10.1055/s-0039-1687841
Bose R, Banerjee S, Dunbar GL (2021) Modeling Neurological Disorders in 3D Organoids Using Human-Derived Pluripotent Stem Cells. Front Cell Dev Biol 9:640212. https://doi.org/10.3389/fcell.2021.640212
Brandner S, Jaunmuktane Z (2017) Prion disease: experimental models and reality. Acta Neuropathol 133(2):197–222. https://doi.org/10.1007/s00401-017-1670-5
Carroll JA, Race B, Williams K, Striebel J, Chesebro B (2018) Microglia are critical in host defense against prion disease. J Virol 92(15). https://doi.org/10.1128/jvi.00549-18
Caughey B, Raymond GJ (1993) Sulfated polyanion inhibition of scrapie-associated PrP accumulation in cultured cells. J Virol 67(2):643–650. https://doi.org/10.1128/JVI.67.2.643-650.1993
Chiaradia I, Lancaster MA (2020) Brain organoids for the study of human neurobiology at the interface of in vitro and in vivo. Nat Neurosci 23(12):1496–1508. https://doi.org/10.1038/s41593-020-00730-3
Choi SH, Kim YH, Hebisch M, Sliwinski C, Lee S, D’Avanzo C, Chen H, Hooli B, Asselin C, Muffat J, Klee JB, Zhang C, Wainger BJ, Peitz M, Kovacs DM, Woolf CJ, Wagner SL, Tanzi RE, Kim DY (2014) A three-dimensional human neural cell culture model of Alzheimer’s disease. Nature 515(7526):274–278. https://doi.org/10.1038/nature13800
Collinge J, Sidle KC, Meads J, Ironside J, Hill AF (1996) Molecular analysis of prion strain variation and the aetiology of “new variant” CJD. Nature 383(6602):685–690. https://doi.org/10.1038/383685a0
Collins SJ, Haigh CL (2017) Simplified Murine 3D Neuronal Cultures for Investigating Neuronal Activity and Neurodegeneration. Cell Biochem Biophys 75(1):3–13. https://doi.org/10.1007/s12013-016-0768-z
Courageot MP, Daude N, Nonno R, Paquet S, Di Bari MA, Le Dur A, Chapuis J, Hill AF, Agrimi U, Laude H, Vilette D (2008) A cell line infectible by prion strains from different species. J Gen Virol 89(Pt 1):341–347. https://doi.org/10.1099/vir.0.83344-0
Cramm M, Schmitz M, Karch A, Mitrova E, Kuhn F, Schroeder B, Raeber A, Varges D, Kim YS, Satoh K, Collins S, Zerr I (2016) Stability and Reproducibility Underscore Utility of RT-QuIC for Diagnosis of Creutzfeldt-Jakob Disease. Mol Neurobiol 53(3):1896–1904. https://doi.org/10.1007/s12035-015-9133-2
Cronier S, Beringue V, Bellon A, Peyrin JM, Laude H (2007) Prion strain- and species-dependent effects of antiprion molecules in primary neuronal cultures. J Virol 81(24):13794–13800. https://doi.org/10.1128/JVI.01502-07
Doh-ura K, Ishikawa K, Murakami-Kubo I, Sasaki K, Mohri S, Race R, Iwaki T (2004) Treatment of transmissible spongiform encephalopathy by intraventricular drug infusion in animal models. J Virol 78(10):4999–5006. https://doi.org/10.1128/jvi.78.10.4999-5006.2004
Duyckaerts C, Potier MC, Delatour B (2008) Alzheimer disease models and human neuropathology: similarities and differences. Acta Neuropathol 115(1):5–38. https://doi.org/10.1007/s00401-007-0312-8
Fair SR, Julian D, Hartlaub AM, Pusuluri ST, Malik G, Summerfied TL, Zhao G, Hester AB, Ackerman WE, Hollingsworth EW, Ali M, McElroy CA, Buhimschi IA, Imitola J, Maitre NL, Bedrosian TA, Hester ME (2020) Electrophysiological Maturation of Cerebral Organoids Correlates with Dynamic Morphological and Cellular Development. Stem Cell Reports 15(4):855–868. https://doi.org/10.1016/j.stemcr.2020.08.017
Falsig J, Aguzzi A (2008) The prion organotypic slice culture assay–POSCA. Nat Protoc 3(4):555–562. https://doi.org/10.1038/nprot.2008.13
Farquhar C, Dickinson A, Bruce M (1999) Prophylactic potential of pentosan polysulphate in transmissible spongiform encephalopathies. Lancet 353(9147):117. https://doi.org/10.1016/S0140-6736(98)05395-1
Fernández-Borges N, Espinosa JC, Marín-Moreno A, Aguilar-Calvo P, Asante E, Kitamoto T, Mohri S, Andréoletti O, Torres JM (2017) Protective Effect of Val<sub>129</sub>-PrP against Bovine Spongiform Encephalopathy but not Variant Creutzfeldt-Jakob Disease. Emerging Infectious Disease Journal 23(9):1522. https://doi.org/10.3201/eid2309.161948
Fevrier B, Vilette D, Archer F, Loew D, Faigle W, Vidal M, Laude H, Raposo G (2004) Cells release prions in association with exosomes. Proc Natl Acad Sci U S A 101(26):9683–9688. https://doi.org/10.1073/pnas.0308413101
Flechsig E, Hegyi I, Enari M, Schwarz P, Collinge J, Weissmann C (2001) Transmission of scrapie by steel-surface-bound prions. Mol Med 7(10):679–684
Foliaki ST, Groveman BR, Yuan J, Walters R, Zhang S, Tesar P, Zou W, Haigh CL (2020) Pathogenic Prion Protein Isoforms Are Not Present in Cerebral Organoids Generated from Asymptomatic Donors Carrying the E200K Mutation Associated with Familial Prion Disease. Pathogens, 9(6). https://doi.org/10.3390/pathogens9060482
Foliaki ST, Schwarz B, Groveman BR, Walters RO, Ferreira NC, Orrù CD, Smith A, Wood A, Schmit OM, Freitag P, Yuan J, Zou W, Bosio CM, Carroll JA, Haigh CL (2021) Neuronal excitatory-to-inhibitory balance is altered in cerebral organoid models of genetic neurological diseases. Mol Brain 14(1):156. https://doi.org/10.1186/s13041-021-00864-w
Frid K, Binyamin O, Fainstein N, Keller G, Ben-Hur T, Gabizon R (2018) Autologous neural progenitor cell transplantation into newborn mice modeling for E200K genetic prion disease delays disease progression. Neurobiol Aging 65:192–200. https://doi.org/10.1016/j.neurobiolaging.2018.01.004
Frid K, Binyamin O, Usman A, Gabizon R (2020) Delay of gCJD aggravation in sick TgMHu2ME199K mice by combining NPC transplantation and Nano-PSO administration. Neurobiol Aging 95:231–239. https://doi.org/10.1016/j.neurobiolaging.2020.07.030
Friedman-Levi Y, Meiner Z, Canello T, Frid K, Kovacs GG, Budka H, Avrahami D, Gabizon R (2011) Fatal prion disease in a mouse model of genetic E200K Creutzfeldt-Jakob disease. PLoS Pathog 7(11):e1002350. https://doi.org/10.1371/journal.ppat.1002350
Geschwind MD (2015) Prion Diseases. Continuum (Minneap Minn), 21(6 Neuroinfectious Disease), 1612–1638. https://doi.org/10.1212/CON.0000000000000251
Ghaemmaghami S, Phuan PW, Perkins B, Ullman J, May BC, Cohen FE, Prusiner SB (2007) Cell division modulates prion accumulation in cultured cells. Proc Natl Acad Sci U S A 104(46):17971–17976. https://doi.org/10.1073/pnas.0708372104
Giandomenico SL, Mierau SB, Gibbons GM, Wenger LMD, Masullo L, Sit T, Sutcliffe M, Boulanger J, Tripodi M, Derivery E, Paulsen O, Lakatos A, Lancaster MA (2019) Cerebral organoids at the air-liquid interface generate diverse nerve tracts with functional output. Nat Neurosci 22(4):669–679. https://doi.org/10.1038/s41593-019-0350-2
Giri RK, Young R, Pitstick R, DeArmond SJ, Prusiner SB, Carlson GA (2006) Prion infection of mouse neurospheres. Proc Natl Acad Sci U S A 103(10):3875–3880. https://doi.org/10.1073/pnas.0510902103
Gonzalez C, Armijo E, Bravo-Alegria J, Becerra-Calixto A, Mays CE, Soto C (2018) Modeling amyloid beta and tau pathology in human cerebral organoids. Mol Psychiatry 23(12):2363–2374. https://doi.org/10.1038/s41380-018-0229-8
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
Groveman BR, Ferreira NC, Foliaki ST, Walters RO, Winkler CW, Race B, Hughson AG, Zanusso G, Haigh CL (2021) Human cerebral organoids as a therapeutic drug screening model for Creutzfeldt-Jakob disease. Sci Rep 11(1):5165. https://doi.org/10.1038/s41598-021-84689-6
Groveman BR, Foliaki ST, Orru CD, Zanusso G, Carroll JA, Race B, Haigh CL (2019) Sporadic Creutzfeldt-Jakob disease prion infection of human cerebral organoids. Acta Neuropathol Commun 7(1):90. https://doi.org/10.1186/s40478-019-0742-2
Groveman BR, Orrú CD, Hughson AG, Bongianni M, Fiorini M, Imperiale D, Ladogana A, Pocchiari M, Zanusso G, Caughey B (2017) Extended and direct evaluation of RT-QuIC assays for Creutzfeldt-Jakob disease diagnosis. Ann Clin Transl Neurol 4(2):139–144. https://doi.org/10.1002/acn3.378
Haigh CL, McGlade AR, Lewis V, Masters CL, Lawson VA, Collins SJ (2011) Acute exposure to prion infection induces transient oxidative stress progressing to be cumulatively deleterious with chronic propagation in vitro. Free Radic Biol Med 51(3):594–608. https://doi.org/10.1016/j.freeradbiomed.2011.03.035
Hernández D, Rooney LA, Daniszewski M, Gulluyan L, Liang HH, Cook AL, Hewitt AW, Pébay A (2021) Culture Variabilities of Human iPSC-Derived Cerebral Organoids Are a Major Issue for the Modelling of Phenotypes Observed in Alzheimer’s Disease. Stem Cell Rev Rep. https://doi.org/10.1007/s12015-021-10147-5
Herva ME, Relaño-Ginés A, Villa A, Torres JM (2010) Prion infection of differentiated neurospheres. J Neurosci Methods 188(2):270–275. https://doi.org/10.1016/j.jneumeth.2010.02.022
Hill AF, Joiner S, Wadsworth JDF, Sidle KCL, Bell JE, Budka H, Ironside JW, Collinge J (2003) Molecular classification of sporadic Creutzfeldt-Jakob disease. Brain 126(6):1333–1346. https://doi.org/10.1093/brain/awg125
Huang WK, Wong SZH, Pather SR, Nguyen PTT, Zhang F, Zhang DY, Zhang Z, Lu L, Fang W, Chen L, Fernandes A, Su Y, Song H, Ming GL (2021) Generation of hypothalamic arcuate organoids from human induced pluripotent stem cells. Cell Stem Cell. https://doi.org/10.1016/j.stem.2021.04.006
Ironside JW, Ritchie DL, Head MW (2017) Prion diseases. Handb Clin Neurol 145:393–403. https://doi.org/10.1016/B978-0-12-802395-2.00028-6
Iwamaru Y, Mathiason CK, Telling GC, Hoover EA (2017) Chronic wasting disease prion infection of differentiated neurospheres. Prion 11(4):277–283. https://doi.org/10.1080/19336896.2017.1336273
Iwamaru Y, Takenouchi T, Imamura M, Shimizu Y, Miyazawa K, Mohri S, Yokoyama T, Kitani H (2013) Prion replication elicits cytopathic changes in differentiated neurosphere cultures. J Virol 87(15):8745–8755. https://doi.org/10.1128/jvi.00572-13
Jackson WS (2014) Selective vulnerability to neurodegenerative disease: the curious case of Prion Protein. Dis Model Mech 7(1):21–29. https://doi.org/10.1242/dmm.012146
Jacob F, Schnoll JG, Song H, Ming GL (2021) Building the brain from scratch: Engineering region-specific brain organoids from human stem cells to study neural development and disease. Curr Top Dev Biol 142:477–530. https://doi.org/10.1016/bs.ctdb.2020.12.011
Kadoshima T, Sakaguchi H, Nakano T, Soen M, Ando S, Eiraku M, Sasai Y (2013) Self-organization of axial polarity, inside-out layer pattern, and species-specific progenitor dynamics in human ES cell-derived neocortex. Proc Natl Acad Sci U S A 110(50):20284–20289. https://doi.org/10.1073/pnas.1315710110
Kaisar MA, Sajja RK, Prasad S, Abhyankar VV, Liles T, Cucullo L (2017) New experimental models of the blood-brain barrier for CNS drug discovery. Expert Opin Drug Discov 12(1):89–103. https://doi.org/10.1080/17460441.2017.1253676
Kazlauskaite J, Pinheiro TJ (2005) Aggregation and fibrillization of prions in lipid membranes. Biochem Soc Symp (72), 211–222. https://doi.org/10.1042/bss0720211
Kim H, Park HJ, Choi H, Chang Y, Park H, Shin J, Kim J, Lengner CJ, Lee YK, Kim J (2019) Modeling G2019S-LRRK2 Sporadic Parkinson’s Disease in 3D Midbrain Organoids. Stem Cell Reports 12(3):518–531. https://doi.org/10.1016/j.stemcr.2019.01.020
Klemm HMJ, Welton JM, Masters CL, Klug GM, Boyd A, Hill AF, Collins SJ, Lawson VA (2012) The prion protein preference of sporadic creutzfeldt-jakob disease subtypes*. J Biol Chem 287(43), 36465–36472. https://doi.org/10.1074/jbc.M112.368803
Knight R (2020) Clinical diagnosis of human prion disease. Prog Mol Biol Transl Sci 175:1–18. https://doi.org/10.1016/bs.pmbts.2020.07.006
Kovalevich J, Langford D (2013) Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology. Methods Mol Biol 1078:9–21. https://doi.org/10.1007/978-1-62703-640-5_2
Krance SH, Luke R, Shenouda M, Israwi AR, Colpitts SJ, Darwish L, Strauss M, Watts JC (2020) Cellular models for discovering prion disease therapeutics: Progress and challenges. J Neurochem 153(2):150–172. https://doi.org/10.1111/jnc.14956
Krejciova Z, Alibhai J, Zhao C, Krencik R, Rzechorzek NM, Ullian EM, Manson J, Ironside JW, Head MW, Chandran S (2017) Human stem cell-derived astrocytes replicate human prions in a PRNP genotype-dependent manner. J Exp Med 214(12):3481–3495. https://doi.org/10.1084/jem.20161547
Ladogana A, Liu Q, Xi YG, Pocchiari M (1995) Proteinase-resistant protein in human neuroblastoma cells infected with brain material from Creutzfeldt-Jakob patient. Lancet 345(8949):594–595. https://doi.org/10.1016/s0140-6736(95)90508-1
Lancaster MA, Knoblich JA (2014) Generation of cerebral organoids from human pluripotent stem cells. Nat Protoc 9(10):2329–2340. https://doi.org/10.1038/nprot.2014.158
Lancaster MA, Renner M, Martin CA, Wenzel D, Bicknell LS, Hurles ME, Homfray T, Penninger JM, Jackson AP, Knoblich JA (2013) Cerebral organoids model human brain development and microcephaly. Nature 501(7467):373–379. https://doi.org/10.1038/nature12517
Lawson VA, Lumicisi B, Welton J, Machalek D, Gouramanis K, Klemm HM, Stewart JD, Masters CL, Hoke DE, Collins SJ, Hill AF (2010) Glycosaminoglycan sulphation affects the seeded misfolding of a mutant prion protein. PLoS ONE 5(8):e12351. https://doi.org/10.1371/journal.pone.0012351
Lawson VA, Vella LJ, Stewart JD, Sharples RA, Klemm H, Machalek DM, Masters CL, Cappai R, Collins SJ, Hill AF (2008) Mouse-adapted sporadic human Creutzfeldt-Jakob disease prions propagate in cell culture. Int J Biochem Cell Biol 40(12):2793–2801. https://doi.org/10.1016/j.biocel.2008.05.024
Lewis V, Hill AF, Haigh CL, Klug GM, Masters CL, Lawson VA, Collins SJ (2009) Increased proportions of C1 truncated prion protein protect against cellular M1000 prion infection. J Neuropathol Exp Neurol 68(10):1125–1135. https://doi.org/10.1097/NEN.0b013e3181b96981
Linden R (2017) The Biological Function of the Prion Protein: A Cell Surface Scaffold of Signaling Modules. Front Mol Neurosci 10:77. https://doi.org/10.3389/fnmol.2017.00077
Llorens F, Thune K, Tahir W, Kanata E, Diaz-Lucena D, Xanthopoulos K, Kovatsi E, Pleschka C, Garcia-Esparcia P, Schmitz M, Ozbay D, Correia S, Correia A, Milosevic I, Andreoletti O, Fernandez-Borges N, Vorberg IM, Glatzel M, Sklaviadis T, Torres JM, Krasemann S, Sanchez-Valle R, Ferrer I, Zerr I (2017) YKL-40 in the brain and cerebrospinal fluid of neurodegenerative dementias. Mol Neurodegener 12(1):83. https://doi.org/10.1186/s13024-017-0226-4
Louey A, Hernández D, Pébay A, Daniszewski M (2021) Automation of Organoid Cultures: Current Protocols and Applications. SLAS Discov 26(9):1138–1147. https://doi.org/10.1177/24725552211024547
Madhavan M, Nevin ZS, Shick HE, Garrison E, Clarkson-Paredes C, Karl M, Clayton BLL, Factor DC, Allan KC, Barbar L, Jain T, Douvaras P, Fossati V, Miller RH, Tesar PJ (2018) Induction of myelinating oligodendrocytes in human cortical spheroids. Nat Methods 15(9):700–706. https://doi.org/10.1038/s41592-018-0081-4
Marton RM, Miura Y, Sloan SA, Li Q, Revah O, Levy RJ, Huguenard JR, Pasca SP (2019) Differentiation and maturation of oligodendrocytes in human three-dimensional neural cultures. Nat Neurosci 22(3):484–491. https://doi.org/10.1038/s41593-018-0316-9
Matamoros-Angles A, Gayosso LM, Richaud-Patin Y, di Domenico A, Vergara C, Hervera A, Sousa A, Fernandez-Borges N, Consiglio A, Gavin R, Lopez de Maturana R, Ferrer I, Lopez de Munain A, Raya A, Castilla J, Sanchez-Pernaute R, Del Rio JA (2018) iPS Cell Cultures from a Gerstmann-Straussler-Scheinker Patient with the Y218N PRNP Mutation Recapitulate tau Pathology. Mol Neurobiol 55(4):3033–3048. https://doi.org/10.1007/s12035-017-0506-6
Minikel EV, Vallabh SM, Lek M, Estrada K, Samocha KE, Sathirapongsasuti JF, McLean CY, Tung JY, Yu LP, Gambetti P, Blevins J, Zhang S, Cohen Y, Chen W, Yamada M, Hamaguchi T, Sanjo N, Mizusawa H, Nakamura Y, Kitamoto T, Collins SJ, Boyd A, Will RG, Knight R, Ponto C, Zerr I, Kraus TF, Eigenbrod S, Giese A, Calero M, de Pedro-Cuesta J, Haïk S, Laplanche JL, Bouaziz-Amar E, Brandel JP, Capellari S, Parchi P, Poleggi A, Ladogana A, O'Donnell-Luria AH, Karczewski KJ, Marshall JL, Boehnke M, Laakso M, Mohlke KL, Kähler A, Chambert K, McCarroll S, Sullivan PF, Hultman CM, Purcell SM, Sklar P, van der Lee SJ, Rozemuller A, Jansen C, Hofman A, Kraaij R, van Rooij JG, Ikram MA, Uitterlinden AG, van Duijn CM, Daly MJ, MacArthur DG (2016) Quantifying prion disease penetrance using large population control cohorts. Sci Transl Med 8(322), 322ra329. https://doi.org/10.1126/scitranslmed.aad5169
Moreno JA, Telling GC (2017) Insights into Mechanisms of Transmission and Pathogenesis from Transgenic Mouse Models of Prion Diseases. Methods Mol Biol 1658:219–252. https://doi.org/10.1007/978-1-4939-7244-9_16
Muguruma K, Nishiyama A, Kawakami H, Hashimoto K, Sasai Y (2015) Self-organization of polarized cerebellar tissue in 3D culture of human pluripotent stem cells. Cell Rep 10(4):537–550. https://doi.org/10.1016/j.celrep.2014.12.051
Ormel PR, Vieira de Sá R, van Bodegraven EJ, Karst H, Harschnitz O, Sneeboer MAM, Johansen LE, van Dijk RE, Scheefhals N, Berdenis van Berlekom A, Ribes Martínez E, Kling S, MacGillavry HD, van den Berg LH, Kahn RS, Hol EM, de Witte LD, Pasterkamp RJ (2018) Microglia innately develop within cerebral organoids. Nat Commun 9(1):4167. https://doi.org/10.1038/s41467-018-06684-2
Orrú CD, Groveman BR, Hughson AG, Zanusso G, Coulthart MB, Caughey B (2015) Rapid and sensitive RT-QuIC detection of human Creutzfeldt-Jakob disease using cerebrospinal fluid. mBio 6(1). https://doi.org/10.1128/mBio.02451-14
Orrú CD, Hughson AG, Groveman BR, Campbell KJ, Anson KJ, Manca M, Kraus A, Caughey B (2016) Factors that improve RT-QuIC detection of prion seeding activity. Viruses 8(5). https://doi.org/10.3390/v8050140
Parchi P, Giese A, Capellari S, Brown P, Schulz-Schaeffer W, Windl O, Zerr I, Budka H, Kopp N, Piccardo P, Poser S, Rojiani A, Streichemberger N, Julien J, Vital C, Ghetti B, Gambetti P, Kretzschmar H (1999) Classification of sporadic Creutzfeldt-Jakob disease based on molecular and phenotypic analysis of 300 subjects. Ann Neurol 46(2), 224–233. https://www.ncbi.nlm.nih.gov/pubmed/10443888
Pellegrini L, Bonfio C, Chadwick J, Begum F, Skehel M, Lancaster MA (2020) Human CNS barrier-forming organoids with cerebrospinal fluid production. Science 369(6500). https://doi.org/10.1126/science.aaz5626
Pham MT, Pollock KM, Rose MD, Cary WA, Stewart HR, Zhou P, Nolta JA, Waldau B (2018) Generation of human vascularized brain organoids. NeuroReport 29(7):588–593. https://doi.org/10.1097/WNR.0000000000001014
Pineau H, Sim V (2020) POSCAbilities: The Application of the Prion Organotypic Slice Culture Assay to Neurodegenerative Disease Research. Biomolecules 10(7). https://doi.org/10.3390/biom10071079
Pineau H, Sim VL (2021) From cell culture to organoids-model systems for investigating prion strain characteristics. Biomolecules 11(1). https://doi.org/10.3390/biom11010106
Priola SA (2018) Cell biology of prion infection. Handb Clin Neurol 153:45–68. https://doi.org/10.1016/B978-0-444-63945-5.00003-9
Qian L, Tcw J (2021). Human iPSC-Based Modeling of Central Nerve System Disorders for Drug Discovery. Int J Mol Sci 22(3). https://doi.org/10.3390/ijms22031203
Qian X, Nguyen HN, Song MM, Hadiono C, Ogden SC, Hammack C, Yao B, Hamersky GR, Jacob F, Zhong C, Yoon KJ, Jeang W, Lin L, Li Y, Thakor J, Berg DA, Zhang C, Kang E, Chickering M, Nauen D, Ho CY, Wen Z, Christian KM, Shi PY, Maher BJ, Wu H, Jin P, Tang H, Song H, Ming GL (2016) Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure. Cell 165(5):1238–1254. https://doi.org/10.1016/j.cell.2016.04.032
Qian X, Su Y, Adam CD, Deutschmann AU, Pather SR, Goldberg EM, Su K, Li S, Lu L, Jacob F, Nguyen PTT, Huh S, Hoke A, Swinford-Jackson SE, Wen Z, Gu X, Pierce RC, Wu H, Briand L. A, Chen HI, Wolf JA, Song H, Ming GL (2020) Sliced human cortical organoids for modeling distinct cortical layer formation. Cell StemCell 26(5), 766–781 e769. https://doi.org/10.1016/j.stem.2020.02.002
Raja WK, Mungenast AE, Lin YT, Ko T, Abdurrob F, Seo J, Tsai LH (2016) Self-Organizing 3D Human Neural Tissue Derived from Induced Pluripotent Stem Cells Recapitulate Alzheimer’s Disease Phenotypes. PLoS ONE 11(9):e0161969. https://doi.org/10.1371/journal.pone.0161969
Renner M, Lancaster MA, Bian S, Choi H, Ku T, Peer A, Chung K, Knoblich JA (2017) Self-organized developmental patterning and differentiation in cerebral organoids. EMBO J 36(10), 1316–1329. https://doi.org/10.15252/embj.201694700
Saito T, Mihira N, Matsuba Y, Sasaguri H, Hashimoto S, Narasimhan S, Zhang B, Murayama S, Higuchi M, Lee VMY, Trojanowski JQ, Saido TC (2019) Humanization of the entire murine Mapt gene provides a murine model of pathological human tau propagation. J Biol Chem 294(34):12754–12765. https://doi.org/10.1074/jbc.RA119.009487
Schweitzer JS, Song B, Herrington TM, Park TY, Lee N, Ko S, Jeon J, Cha Y, Kim K, Li Q, Henchcliffe C, Kaplitt M, Neff C, Rapalino O, Seo H, Lee IH, Kim J, Kim T, Petsko GA, Ritz J, Cohen BM, Kong SW, Leblanc P, Carter BS, Kim KS (2020) Personalized iPSC-Derived Dopamine Progenitor Cells for Parkinson’s Disease. N Engl J Med 382(20):1926–1932. https://doi.org/10.1056/NEJMoa1915872
Shaker MR, Pietrogrande G, Martin S, Lee JH, Sun W, Wolvetang EJ (2021) Rapid and Efficient Generation of Myelinating Human Oligodendrocytes in Organoids. Front Cell Neurosci 15:631548. https://doi.org/10.3389/fncel.2021.631548
Slanzi A, Iannoto G, Rossi B, Zenaro E, Constantin G (2020) In vitro Models of Neurodegenerative Diseases. Front Cell Dev Biol 8:328. https://doi.org/10.3389/fcell.2020.00328
Sloan SA, Darmanis S, Huber N, Khan TA, Birey F, Caneda C, Reimer R, Quake SR, Barres BA, Pasca SP (2017) Human Astrocyte Maturation Captured in 3D Cerebral Cortical Spheroids Derived from Pluripotent Stem Cells. Neuron 95(4), 779–790 e776. https://doi.org/10.1016/j.neuron.2017.07.035
Smits LM, Reinhardt L, Reinhardt P, Glatza M, Monzel AS, Stanslowsky N, Rosato-Siri MD, Zanon A, Antony PM, Bellmann J, Nicklas SM, Hemmer K, Qing X, Berger E, Kalmbach N, Ehrlich M, Bolognin S, Hicks AA, Wegner F, Sterneckert JL, Schwamborn JC (2019) Modeling Parkinson’s disease in midbrain-like organoids. NPJ Parkinsons Dis 5:5. https://doi.org/10.1038/s41531-019-0078-4
Tanaka Y, Cakir B, Xiang Y, Sullivan GJ, Park IH (2020) Synthetic Analyses of Single-Cell Transcriptomes from Multiple Brain Organoids and Fetal Brain. Cell Rep 30(6), 1682–1689 e1683. https://doi.org/10.1016/j.celrep.2020.01.038
Tasnim K, Liu J (2021) Emerging bioelectronics for brain organoid electrophysiology. J Mol Biol 167165. https://doi.org/10.1016/j.jmb.2021.167165
Tejchman A, Znoj A, Chlebanowska P, Fraczek-Szczypta A, Majka M (2020) Carbon Fibers as a New Type of Scaffold for Midbrain Organoid Development. Int J Mol Sci 21(17). https://doi.org/10.3390/ijms21175959
Telling GC, Scott M, Hsiao KK, Foster D, Yang SL, Torchia M, Sidle KC, Collinge J, DeArmond SJ, Prusiner SB (1994) Transmission of Creutzfeldt-Jakob disease from humans to transgenic mice expressing chimeric human-mouse prion protein. Proc Natl Acad Sci U S A 91(21):9936–9940. https://doi.org/10.1073/pnas.91.21.9936
Velasco S, Kedaigle AJ, Simmons SK, Nash A, Rocha M, Quadrato G, Paulsen B, Nguyen L, Adiconis X, Regev A, Levin JZ, Arlotta P (2019) Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature 570(7762):523–527. https://doi.org/10.1038/s41586-019-1289-x
Vella LJ, Sharples RA, Lawson VA, Masters CL, Cappai R, Hill AF (2007) Packaging of prions into exosomes is associated with a novel pathway of PrP processing. J Pathol 211(5):582–590. https://doi.org/10.1002/path.2145
Wälzlein JH, Schwenke KA, Beekes M (2021) Propagation of CJD prions in primary murine glia cells expressing human PrP(c). Pathogens 10(8). https://doi.org/10.3390/pathogens10081060
Watanabe M, Buth JE, Vishlaghi N, de la Torre-Ubieta L, Taxidis J, Khakh BS, Coppola G, Pearson CA, Yamauchi K, Gong D, Dai X, Damoiseaux R, Aliyari R, Liebscher S, Schenke-Layland K, Caneda C, Huang EJ, Zhang Y, Cheng G, Geschwind DH, Golshani P, Sun R, Novitch BG (2017) Self-Organized Cerebral Organoids with Human-Specific Features Predict Effective Drugs to Combat Zika Virus Infection. Cell Rep 21(2):517–532. https://doi.org/10.1016/j.celrep.2017.09.047
Wieser HG, Schindler K, Zumsteg D (2006) EEG in Creutzfeldt-Jakob disease. Clin Neurophysiol 117(5):935–951. https://doi.org/10.1016/j.clinph.2005.12.007
Xiang Y, Tanaka Y, Cakir B, Patterson B, Kim KY, Sun P, Kang YJ, Zhong M, Liu X, Patra P, Lee SH, Weissman SM, Park IH (2019) hESC-Derived Thalamic Organoids Form Reciprocal Projections When Fused with Cortical Organoids. Cell Stem Cell 24(3):487-497.e487. https://doi.org/10.1016/j.stem.2018.12.015
Yakoub AM (2019) Cerebral organoids exhibit mature neurons and astrocytes and recapitulate electrophysiological activity of the human brain. Neural Regen Res 14(5):757–761. https://doi.org/10.4103/1673-5374.249283
Zhu C, Herrmann US, Falsig J, Abakumova I, Nuvolone M, Schwarz P, Frauenknecht K, Rushing EJ, Aguzzi A (2016) A neuroprotective role for microglia in prion diseases. J Exp Med 213(6):1047–1059. https://doi.org/10.1084/jem.20151000
Zobeley E, Flechsig E, Cozzio A, Enari M, Weissmann C (1999) Infectivity of scrapie prions bound to a stainless steel surface. Mol Med 5(4):240–243
Acknowledgements
This work was funded by the intramural program of the National Institute of Allergy and Infectious Diseases (National Institutes of Health). The authors would like to thank Dr Roger Moore and Dr Simote Foliaki for critical review of the manuscript.
Funding
This work was funded by the National Institute of Allergy and Infectious Diseases (NIH).
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical approval
Not applicable. No experiments were conducted for this review article.
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Walters, R.O., Haigh, C.L. Organoids for modeling prion diseases. Cell Tissue Res 392, 97–111 (2023). https://doi.org/10.1007/s00441-022-03589-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00441-022-03589-x