{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T23:05:29Z","timestamp":1790809529437,"version":"4.1.0"},"reference-count":131,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T00:00:00Z","timestamp":1701129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Brain organoids are self\u2010organized, three\u2010dimensional (3D) aggregates derived from pluripotent stem cells that have cell types and cellular architectures resembling those of the developing human brain. The current understanding of human brain developmental processes and neurological disorders has advanced significantly with the introduction of this in vitro model. Brain organoids serve as a translational link between two\u2010dimensional (2D) cultures and in vivo models which imitate the neural tube formation at the early and late stages and the differentiation of neuroepithelium with whole\u2010brain regionalization. In addition, the generation of region\u2010specific brain organoids made it possible to investigate the pathogenic and etiological aspects of acquired and inherited brain disease along with drug discovery and drug toxicity testing. In this review article, we first summarize an overview of the existing methods and platforms used for generating brain organoids and their limitations and then discuss the recent advancement in brain organoid technology. In addition, we discuss how brain organoids have been used to model aspects of neurodevelopmental and neurodegenerative diseases, including autism spectrum disorder (ASD), Rett syndrome, Zika virus\u2010related microcephaly, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD).<\/jats:p>","DOI":"10.1002\/bit.28606","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T03:23:55Z","timestamp":1701141835000},"page":"489-506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Brain organoids: A revolutionary tool for modeling neurological disorders and development of therapeutics"],"prefix":"10.1002","volume":"121","author":[{"given":"Prabha","family":"Acharya","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na Young","family":"Choi","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas Denton Texas USA"},{"name":"Department of Healthcare Information Technology Inje University Gimhae Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sunil","family":"Shrestha","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4174-0219","authenticated-orcid":false,"given":"Sehoon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Healthcare Information Technology Inje University Gimhae Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moo\u2010Yeal","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering University of North Texas Denton Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,28]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00213-013-3332-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/5086250"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/2193-1801-4-S1-L49"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.05.022"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4304"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)69041-7"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddv166"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.590119"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2011.06.039"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.2989"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.04.028"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22330"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00308809"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics14112301"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1529"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/brv.12626"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24662"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202101462"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr093"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21030694"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24775-5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-016-0274-8"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature13800"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1715865115"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-63265-4.00005-4"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18296"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.04.014"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-24358-4"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn.2017.107"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcs.1398"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms7500"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09941"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2008.09.002"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3312"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2019.00558"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07287"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3039"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tics.2011.07.003"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41593-019-0350-2"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41596-020-00433-w"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.610427"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-018-0229-8"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/S12861-019-0183-Y\/FIGURES\/4"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2019.00039"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10013"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.10.079"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/gene.10183"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.15283\/IJSC22004"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpsc.65"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.28810"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/cercor\/bhp029"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.07.005"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1315710110"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/adhm.202302502"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41567-018-0046-7"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2017.09.021"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ydbio.2016.06.037"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.05.022"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-010-9138-1"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.01.020"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stemcr.2019.04.011"},{"key":"e_1_2_9_63_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2021.102063"},{"key":"e_1_2_9_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/2040-2392-3-9"},{"key":"e_1_2_9_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2021.109042"},{"key":"e_1_2_9_66_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.3906"},{"key":"e_1_2_9_67_1","doi-asserted-by":"crossref","unstructured":"Lancaster M. A. &Knoblich J. A.(2014).Generation of cerebral organoids from human pluripotent stem cells.9(10) 2329\u20132340.https:\/\/doi.org\/10.1038\/nprot.2014.158","DOI":"10.1038\/nprot.2014.158"},{"key":"e_1_2_9_68_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12517"},{"key":"e_1_2_9_69_1","doi-asserted-by":"crossref","unstructured":"Lang M.\u2010F. Shi Y. Ciccolini F. &Davy A.(2012).Dynamic roles of microRNAs in neurogenesis.https:\/\/doi.org\/10.3389\/fnins.2012.00071","DOI":"10.3389\/fnins.2012.00071"},{"key":"e_1_2_9_70_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201592372"},{"key":"e_1_2_9_71_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.127.3.457"},{"key":"e_1_2_9_72_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature05453"},{"key":"e_1_2_9_73_1","doi-asserted-by":"publisher","DOI":"10.1101\/2023.02.16.528892"},{"key":"e_1_2_9_74_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2018.05.008"},{"key":"e_1_2_9_75_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2009-10-10-r104"},{"key":"e_1_2_9_76_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.4127"},{"key":"e_1_2_9_77_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.06.034"},{"key":"e_1_2_9_78_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21218290"},{"key":"e_1_2_9_79_1","doi-asserted-by":"publisher","DOI":"10.3389\/fped.2019.00225"},{"key":"e_1_2_9_80_1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2017.86"},{"key":"e_1_2_9_81_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.097212"},{"key":"e_1_2_9_82_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejmoa1600651"},{"key":"e_1_2_9_83_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2014.12.051"},{"key":"e_1_2_9_84_1","doi-asserted-by":"publisher","DOI":"10.1177\/1073858403260995"},{"key":"e_1_2_9_85_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25032"},{"key":"e_1_2_9_86_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau5729"},{"key":"e_1_2_9_87_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-04358-6"},{"key":"e_1_2_9_88_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz5626"},{"key":"e_1_2_9_89_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0000000000001014"},{"key":"e_1_2_9_90_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2017.152"},{"key":"e_1_2_9_91_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.140707"},{"key":"e_1_2_9_92_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.04.032"},{"key":"e_1_2_9_93_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.166074"},{"key":"e_1_2_9_94_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2020.02.002"},{"key":"e_1_2_9_95_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature22047"},{"key":"e_1_2_9_96_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0161969"},{"key":"e_1_2_9_97_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-022-00929-5"},{"key":"e_1_2_9_98_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep40920"},{"key":"e_1_2_9_99_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003-023-04547-1"},{"key":"e_1_2_9_100_1","doi-asserted-by":"publisher","DOI":"10.1111\/EJN.14081"},{"key":"e_1_2_9_101_1","doi-asserted-by":"publisher","DOI":"10.1039\/d1lc00535a"},{"key":"e_1_2_9_102_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3041"},{"key":"e_1_2_9_103_1","doi-asserted-by":"publisher","DOI":"10.1042\/EBC20200150"},{"key":"e_1_2_9_104_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-020-0566-4"},{"key":"e_1_2_9_105_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.27797"},{"key":"e_1_2_9_106_1","doi-asserted-by":"crossref","unstructured":"Smits L. M. Reinhardt L. Reinhardt P. Glatza M. Monzel A. S. Stanslowsky N. Rosato\u2010siri M. D. Zanon A. Antony P. M. Bellmann J. Nicklas S. M. Hemmer K. Qing X. Berger E. Kalmbach N. Ehrlich M. Bolognin S. Hicks A. A. Wegner F. \u2026Schwamborn J. C.(2019).Modeling Parkinson' s diseasein midbrain\u2010like organoids.August2018.","DOI":"10.1038\/s41531-019-0078-4"},{"key":"e_1_2_9_107_1","doi-asserted-by":"publisher","DOI":"10.1002\/btm2.10378"},{"key":"e_1_2_9_108_1","unstructured":"Szeb\u00e9nyi K. Wenger L. M. D. Sun Y. Dunn A. W. E. Limegrover C. A. Gibbons G. M. Conci E. Paulsen O. Mierau S. B. Balmus G. &Lakatos A.(2021).Neuronal pathology."},{"key":"e_1_2_9_109_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.24.4959"},{"key":"e_1_2_9_110_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202012523"},{"key":"e_1_2_9_111_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380-021-01243-6"},{"key":"e_1_2_9_112_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136541"},{"key":"e_1_2_9_113_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1289-x"},{"key":"e_1_2_9_114_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41378-020-00185-3"},{"key":"e_1_2_9_115_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)00006-4"},{"key":"e_1_2_9_116_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics13020280"},{"key":"e_1_2_9_117_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"e_1_2_9_118_1","doi-asserted-by":"crossref","unstructured":"Wang P. Mokhtari R. Pedrosa E. Kirschenbaum M. Bayrak C. Zheng D. &Lachman H. M.(2017).CRISPR\/Cas9\u2010mediated heterozygous knockout of the autism gene CHD8 and characterization of its transcriptional networks in cerebral organoids derived from iPS cells.1\u201317.https:\/\/doi.org\/10.1186\/s13229-017-0124-1","DOI":"10.1186\/s13229-017-0124-1"},{"key":"e_1_2_9_119_1","article-title":"Modeling autism\u2010associated SHANK3 deficiency using human cortico\u2010striatal organoids generated from single neural rosettes","author":"Wang Y.","year":"2021","journal-title":"BioRxiv"},{"key":"e_1_2_9_120_1","doi-asserted-by":"publisher","DOI":"10.1038\/NN1402"},{"key":"e_1_2_9_121_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.09.047"},{"key":"e_1_2_9_122_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcdb.2020.05.012"},{"key":"e_1_2_9_123_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2018.12.015"},{"key":"e_1_2_9_124_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.07.007"},{"key":"e_1_2_9_125_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4184"},{"key":"e_1_2_9_126_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.tea.2017.0423"},{"key":"e_1_2_9_127_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.12.005"},{"key":"e_1_2_9_128_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt780"},{"key":"e_1_2_9_129_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biomaterials.2013.11.028"},{"key":"e_1_2_9_130_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1201-1129"},{"key":"e_1_2_9_131_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19264-0"},{"key":"e_1_2_9_132_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.06.017"}],"container-title":["Biotechnology and Bioengineering"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/bit.28606","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T19:23:55Z","timestamp":1760037835000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/bit.28606"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,28]]},"references-count":131,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/bit.28606"],"URL":"https:\/\/doi.org\/10.1002\/bit.28606","archive":["Portico"],"relation":{},"ISSN":["0006-3592","1097-0290"],"issn-type":[{"value":"0006-3592","type":"print"},{"value":"1097-0290","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,28]]},"assertion":[{"value":"2023-05-01","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-06","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}