Cerebral organoids: emerging ex vivo humanoid models of glioblastoma
Tóm tắt
Glioblastoma is an aggressive form of brain cancer that has seen only marginal improvements in its bleak survival outlook of 12–15 months over the last forty years. There is therefore an urgent need for the development of advanced drug screening platforms and systems that can better recapitulate glioblastoma’s infiltrative biology, a process largely responsible for its relentless propensity for recurrence and progression. Recent advances in stem cell biology have allowed the generation of artificial tridimensional brain-like tissue termed cerebral organoids. In addition to their potential to model brain development, these reagents are providing much needed synthetic humanoid scaffolds to model glioblastoma’s infiltrative capacity in a faithful and scalable manner. Here, we highlight and review the early breakthroughs in this growing field and discuss its potential future role for glioblastoma research.
Tài liệu tham khảo
Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE et al (2014) The epidemiology of glioma in adults: a state of the science review. Neuro Oncol 16:896–913. https://doi.org/10.1093/neuonc/nou087
Delgado-López PD, Corrales-García EM (2016) Survival in glioblastoma: a review on the impact of treatment modalities. Clin Transl Oncol 18:1062–1071. https://doi.org/10.1007/s12094-016-1497-x
Chen J, Li Y, Yu TS, McKay RM, Burns DK, Kernie SG et al (2012) A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488:522–526. https://doi.org/10.1038/nature11287
Eramo A, Ricci-Vitiani L, Zeuner A, Pallini R, Lotti F, Sette G et al (2006) Chemotherapy resistance of glioblastoma stem cells [2]. Cell Death Differ 13:1238–1241. https://doi.org/10.1038/sj.cdd.4401872
Paolillo M, Boselli C, Schinelli S (2018) Glioblastoma under siege: an overview of current therapeutic strategies. Brain Sci 8:15. https://doi.org/10.3390/brainsci8010015
Galli R, Binda E, Orfanelli U, Cipelletti B, Gritti A, De Vitis S et al (2004) Isolation and characterization of tumorigenic, stem-like neural precursors from human glioblastoma (Cancer Research (October 2004) 64 (7011-7021). Cancer Res 64:8130
Singh SK, Hawkins C, Clarke ID, Squire JA, Bayani J, Hide T et al (2004) Identification of human brain tumour initiating cells. Nature 432:396–401. https://doi.org/10.1038/nature03128
Pollard SM, Yoshikawa K, Clarke ID, Danovi D, Stricker S, Russell R et al (2009) Glioma stem cell lines expanded in adherent culture have tumor-specific phenotypes and are suitable for chemical and genetic screens. Cell Stem Cell 4:568–580. https://doi.org/10.1016/j.stem.2009.03.014
Zanders ED, Svensson F, Bailey DS (2019) Therapy for glioblastoma: is it working? Drug Discov Today 24:1193–1201. https://doi.org/10.1016/j.drudis.2019.03.008
Monje M, Borniger JC, D’Silva NJ, Deneen B, Dirks PB, Fattahi F et al (2020) Roadmap for the emerging field of cancer neuroscience. Cell 181:219–222. https://doi.org/10.1016/j.cell.2020.03.034
Venkataramani V, Tanev DI, Strahle C, Studier-Fischer A, Fankhauser L, Kessler T et al (2019) Glutamatergic synaptic input to glioma cells drives brain tumour progression. Nature 573:532–538. https://doi.org/10.1038/s41586-019-1564-x
Venkatesh HS, Morishita W, Geraghty AC, Silverbush D, Gillespie SM, Arzt M et al (2019) Electrical and synaptic integration of glioma into neural circuits. Nature 573:539–545. https://doi.org/10.1038/s41586-019-1563-y
Schuhmacher AJ, Squatrito M (2017) Animal models in glioblastoma: use in biology and developing therapeutic strategies. In: Somasundaram K (ed) Advances in biology and treatment of glioblastoma. Current Cancer Research. Springer, Cham, pp 219–240. https://doi.org/10.1007/978-3-319-56820-1_9
Lui JH, Hansen DV, Kriegstein AR (2011) Development and evolution of the human neocortex. Cell 146:18–36. https://doi.org/10.1016/j.cell.2011.06.030
Hackam DG, Redelmeier DA (2006) Translation of research evidence from animals to humans. JAMA 296:1727. https://doi.org/10.1001/jama.296.14.1731
Shanks N, Greek R, Greek J (2009) Are animal models predictive for humans? Philos Ethics Humanit Med 4:1–20. https://doi.org/10.1186/1747-5341-4-2
van der Worp HB, Howells DW, Sena ES, Porritt MJ, Rewell S, O’Collins V et al (2010) Can animal models of disease reliably inform human studies? PLoS Med 7:e1000245. https://doi.org/10.1371/journal.pmed.1000245
Ben-David U, Ha G, Tseng YY, Greenwald NF, Oh C, Shih J et al (2017) Patient-derived xenografts undergo mouse-specific tumor evolution. Nat Genet 49:1567–1575. https://doi.org/10.1038/ng.3967
Herrera-Perez M, Voytik-Harbin SL, Rickus JL (2015) Extracellular matrix properties regulate the migratory response of glioblastoma stem cells in three-dimensional culture. Tissue Eng Part A 21:2572–2582. https://doi.org/10.1089/ten.tea.2014.0504
Hubert CG, Rivera M, Spangler LC, Wu Q, Mack SC, Prager BC et al (2016) A three-dimensional organoid culture system derived from human glioblastomas recapitulates the hypoxic gradients and cancer stem cell heterogeneity of tumors found in vivo. Cancer Res 76:2465–2477. https://doi.org/10.1158/0008-5472.CAN-15-2402
Jacob F, Salinas RD, Zhang DY, Nguyen PTT, Schnoll JG, Wong SZH et al (2020) A patient-derived glioblastoma organoid model and biobank recapitulates inter- and intra-tumoral heterogeneity. Cell 180:188–204.e22. https://doi.org/10.1016/j.cell.2019.11.036
Nayernia Z, Turchi L, Cosset E, Peterson H, Dutoit V, Dietrich PY et al (2013) The relationship between brain tumor cell invasion of engineered neural tissues and invivo features of glioblastoma. Biomaterials 34:8279–8290. https://doi.org/10.1016/j.biomaterials.2013.07.006
Plummer S, Wallace S, Ball G, Lloyd R, Schiapparelli P, Quiñones-Hinojosa A et al (2019) A human iPSC-derived 3D platform using primary brain cancer cells to study drug development and personalized medicine. Sci Rep 9:1–11. https://doi.org/10.1038/s41598-018-38130-0
Pamies D, Barreras P, Block K, Makri G, Kumar A, Wiersma D et al (2017) A human brain microphysiological system derived from induced pluripotent stem cells to study neurological diseases and toxicity. ALTEX 34:362–376. https://doi.org/10.14573/altex.1609122
Quadrato G, Nguyen T, Macosko EZ, Sherwood JL, Yang SM, Berger DR et al (2017) Cell diversity and network dynamics in photosensitive human brain organoids. Nature 545:48–53. https://doi.org/10.1038/nature22047
Velasco S, Kedaigle AJ, Simmons SK, Nash A, Rocha M, Quadrato G et al (2019) Individual brain organoids reproducibly form cell diversity of the human cerebral cortex. Nature 570:523–527. https://doi.org/10.1038/s41586-019-1289-x
Lancaster MA, Corsini NS, Wolfinger S, Gustafson EH, Phillips AW, Burkard TR et al (2017) Guided self-organization and cortical plate formation in human brain organoids. Nat Biotechnol 35:659–666. https://doi.org/10.1038/nbt.3906
Li Y, Muffat J, Omer A, Bosch I, Lancaster MA, Sur M et al (2017) Induction of expansion and folding in human cerebral organoids. Cell Stem Cell 20:385–396.e3. https://doi.org/10.1016/j.stem.2016.11.017
Pellegrini L, Bonfio C, Chadwick J, Begum F, Skehel M, Lancaster MA (2020) Human CNS barrier-forming organoids with cerebrospinal fluid production. Science (80-) 5626:eaaz5626. https://doi.org/10.1126/science.aaz5626
Qian X, Song H, Ming GL (2019) Brain organoids: advances, applications and challenges. Dev. https://doi.org/10.1242/dev.166074
Bian S, Repic M, Guo Z, Kavirayani A, Burkard T, Bagley JA et al (2018) Genetically engineered cerebral organoids model brain tumor formation. Nat Methods 15:631–639. https://doi.org/10.1038/s41592-018-0070-7
Ogawa J, Pao GM, Shokhirev MN, Verma IM (2018) Glioblastoma model using human cerebral organoids. Cell Rep 23:1220–1229. https://doi.org/10.1016/j.celrep.2018.03.105
Ortensi B, Setti M, Osti D, Pelicci G (2013) Cancer stem cell contribution to glioblastoma invasiveness. Stem Cell Res Ther 4:1–11. https://doi.org/10.1186/scrt166
Bhaduri A, Di Lullo E, Jung D, Müller S, Crouch EE, Espinosa CS et al (2020) Outer radial glia-like cancer stem cells contribute to heterogeneity of glioblastoma. Cell Stem Cell 26:48–63.e6. https://doi.org/10.1016/j.stem.2019.11.015
Krieger TG, Tirier SM, Park J, Jechow K, Eisemann T, Peterziel H et al (2020) Modeling glioblastoma invasion using human brain organoids and single-cell transcriptomics. Neuro Oncol. https://doi.org/10.1093/neuonc/noaa091
Linkous A, Balamatsias D, Snuderl M, Edwards L, Miyaguchi K, Milner T et al (2019) Modeling patient-derived glioblastoma with cerebral organoids. Cell Rep 26:3203–3211.e5. https://doi.org/10.1016/j.celrep.2019.02.063
Pine AR, Cirigliano SM, Nicholson JG, Hu Y, Linkous A, Miyaguchi K et al (2020) Tumor microenvironment is critical for the maintenance of cellular states found in primary glioblastomas. Cancer Discov. https://doi.org/10.1158/2159-8290.cd-20-0057
da Silva B, Mathew RK, Polson ES, Williams J, Wurdak H (2018) Spontaneous glioblastoma spheroid infiltration of early-stage cerebral organoids models brain tumor invasion. SLAS Discov 23:862–868. https://doi.org/10.1177/2472555218764623
Bagley JA, Reumann D, Bian S, Lévi-Strauss J, Knoblich JA (2017) Fused cerebral organoids model interactions between brain regions. Nat Methods 14:743–751. https://doi.org/10.1038/nmeth.4304
Hodge RD, Bakken TE, Miller JA, Smith KA, Barkan ER, Graybuck LT et al (2019) Conserved cell types with divergent features in human versus mouse cortex. Nature 573:61–68. https://doi.org/10.1038/s41586-019-1506-7
Osswald M, Jung E, Sahm F, Solecki G, Venkataramani V, Blaes J et al (2015) Brain tumour cells interconnect to a functional and resistant network. Nature 528:93–98. https://doi.org/10.1038/nature16071
The Cancer Genome Atlas Research Network (2008) Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455:1061–1068. https://doi.org/10.1038/nature07385
Verhaak RGW, Hoadley KA, Purdom E, Wang V, Qi Y, Wilkerson MD et al (2010) Integrated genomic analysis identifies clinically relevant subtypes of glioblastoma characterized by abnormalities in PDGFRA, IDH1, EGFR, and NF1. Cancer Cell 17:98–110. https://doi.org/10.1016/j.ccr.2009.12.020
Kratochvil MJ, Seymour AJ, Li TL, Paşca SP, Kuo CJ, Heilshorn SC (2019) Engineered materials for organoid systems. Nat Rev Mater 4:606–622. https://doi.org/10.1038/s41578-019-0129-9
Yoon SJ, Elahi LS, Pașca AM, Marton RM, Gordon A, Revah O et al (2019) Reliability of human cortical organoid generation. Nat Methods 16:75–78. https://doi.org/10.1038/s41592-018-0255-0
Jacob F, Pather SR, Huang WK, Zhang F, Wong SZH, Zhou H et al (2020) Human pluripotent stem cell-derived neural cells and brain organoids reveal SARS-CoV-2 neurotropism predominates in choroid plexus epithelium. Cell Stem Cell 27:1–14. https://doi.org/10.1016/j.stem.2020.09.016
Sivitilli AA, Gosio JT, Ghoshal B, Evstratova A, Trcka D, Ghiasi P et al (2020) Robust production of uniform human cerebral organoids from pluripotent stem cells. Life Sci Alliance 3:1–10. https://doi.org/10.26508/lsa.202000707
Farin A, Suzuki SO, Weiker M, Goldman JE, Bruce JN, Canoll P (2006) Transplanted glioma cells migrate and proliferate on host brain vasculature: a dynamic analysis. Glia 53:799–808. https://doi.org/10.1002/glia.20334
Infanger DW, Cho YJ, Lopez BS, Mohanan S, Liu SC, Gursel D et al (2013) Glioblastoma stem cells are regulated by interleukin-8 signaling in a tumoral perivascular niche. Cancer Res 73:7079–7089. https://doi.org/10.1158/0008-5472.CAN-13-1355
Ham O, Jin YB, Kim J, Lee MO (2020) Blood vessel formation in cerebral organoids formed from human embryonic stem cells. Biochem Biophys Res Commun 521:84–90. https://doi.org/10.1016/j.bbrc.2019.10.079
Cakir B, Xiang Y, Tanaka Y, Kural MH, Parent M, Kang YJ et al (2019) Engineering of human brain organoids with a functional vascular-like system. Nat Methods 16:1169–1175. https://doi.org/10.1038/s41592-019-0586-5
Pham MT, Pollock KM, Rose MD, Cary WA, Stewart HR, Zhou P et al (2018) Generation of human vascularized brain organoids. Neuroreport 29:588–593. https://doi.org/10.1097/WNR.0000000000001014
Ormel PR, Vieira de Sá R, van Bodegraven EJ, Karst H, Harschnitz O, Sneeboer MAM et al (2018) Microglia innately develop within cerebral organoids. Nat Commun. https://doi.org/10.1038/s41467-018-06684-2
Song L, Yuan X, Jones Z, Vied C, Miao Y, Marzano M et al (2019) Functionalization of brain region-specific spheroids with isogenic microglia-like cells. Sci Rep 9:1–18. https://doi.org/10.1038/s41598-019-47444-6
Abud EM, Ramirez RN, Martinez ES, Healy LM, Nguyen CHH, Newman SA et al (2017) iPSC-derived human microglia-like cells to study neurological diseases. Neuron 94:278–293.e9. https://doi.org/10.1016/j.neuron.2017.03.042
Muffat J, Li Y, Yuan B, Mitalipova M, Omer A, Corcoran S et al (2016) Efficient derivation of microglia-like cells from human pluripotent stem cells. Nat Med 22:1358–1367. https://doi.org/10.1038/nm.4189
Cao X, Yakala GK, van den Hil FE, Cochrane A, Mummery CL, Orlova VV (2019) Differentiation and functional comparison of monocytes and macrophages from hiPSCs with peripheral blood derivatives. Stem Cell Rep 12:1282–1297. https://doi.org/10.1016/j.stemcr.2019.05.003
Montel-Hagen A, Seet CS, Li S, Chick B, Zhu Y, Chang P et al (2019) Organoid-induced differentiation of conventional T cells from human pluripotent stem cells. Cell Stem Cell 24:376–389.e8. https://doi.org/10.1016/j.stem.2018.12.011
Lachmann N, Ackermann M, Frenzel E, Liebhaber S, Brennig S, Happle C et al (2015) Large-scale hematopoietic differentiation of human induced pluripotent stem cells provides granulocytes or macrophages for cell replacement therapies. Stem Cell Rep 4:282–296. https://doi.org/10.1016/j.stemcr.2015.01.005
Tejero R, Huang Y, Katsyv I, Kluge M, Lin JY, Tome-Garcia J et al (2019) Gene signatures of quiescent glioblastoma cells reveal mesenchymal shift and interactions with niche microenvironment. EBioMedicine 42:252–269. https://doi.org/10.1016/j.ebiom.2019.03.064
Frisira E, Rashid F, Varma SN, Badodi S, Benjamin-Ombo VA, Michod D et al (2019) NPI-0052 and γ-radiation induce a synergistic apoptotic effect in medulloblastoma. Cell Death Dis. https://doi.org/10.1038/s41419-019-2026-y
Ghatak S, Dolatabadi N, Gao R, Wu Y, Scott H, Trudler D et al (2020) NitroSynapsin ameliorates hypersynchronous neural network activity in Alzheimer hiPSC models. Mol Psychiatry. https://doi.org/10.1038/s41380-020-0776-7
Grenier K, Kao J, Diamandis P (2020) Three-dimensional modeling of human neurodegeneration: brain organoids coming of age. Mol Psychiatry 25:254–274. https://doi.org/10.1038/s41380-019-0500-7
Bershteyn M, Nowakowski TJ, Pollen AA, Di Lullo E, Nene A, Wynshaw-Boris A et al (2017) Human iPSC-derived cerebral organoids model cellular features of lissencephaly and reveal prolonged mitosis of outer radial glia. Cell Stem Cell 20:435–449.e4. https://doi.org/10.1016/j.stem.2016.12.007
Iefremova V, Manikakis G, Krefft O, Jabali A, Weynans K, Wilkens R et al (2017) An organoid-based model of cortical development identifies non-cell-autonomous defects in Wnt signaling contributing to miller-dieker syndrome. Cell Rep 19:50–59. https://doi.org/10.1016/j.celrep.2017.03.047
Goranci-Buzhala G, Mariappan A, Gabriel E, Ramani A, Ricci-Vitiani L, Buccarelli M et al (2020) Rapid and efficient invasion assay of glioblastoma in human brain organoids. Cell Rep 31:107738. https://doi.org/10.1016/j.celrep.2020.107738
Neftel C, Laffy J, Filbin MG, Hara T, Shore ME, Rahme GJ et al (2019) An integrative model of cellular states, plasticity, and genetics for glioblastoma. Cell 178:835–849.e21. https://doi.org/10.1016/j.cell.2019.06.024