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dc.contributor.authorHarding, Alfred T.
dc.contributor.authorGehrke, Lee
dc.contributor.authorVyas, Jatin M.
dc.contributor.authorHarding, Hannah Brown
dc.date.accessioned2025-07-30T20:00:51Z
dc.date.available2025-07-30T20:00:51Z
dc.date.issued2025-07-19
dc.identifier.urihttps://hdl.handle.net/1721.1/162172
dc.description.abstractWith the rise in immunocompromised individuals and patients with immune-related comorbidities such as COVID-19, the rate of fungal infections is growing. This increase, along with the current plateau in antifungal drug development, has made understanding the pathogenesis and dissemination of these organisms more pertinent than ever. The mouse model of fungal infection, while informative on a basic scientific level, has severe limitations in terms of translation to the human disease. Here we present data supporting the implementation of the human cerebral organoid model, which is generated from human embryonic stem cells and accurately recapitulates relevant brain cell types and structures, to study fungal infection and dissemination to the central nervous system (CNS). This approach provides direct insight into the relevant pathogenesis of specific fungal organisms in human tissues where in vivo models are impossible. With this model system we assessed the specific brain tropisms and cellular effects of fungal pathogens known to cross the blood–brain barrier (BBB), such as Cryptococcus neoformans. We determined the effects of this fungal pathogen on the overall gross morphology, cellular architecture, and cytokine release from these model organoids. Furthermore, we demonstrated that C. neoformans penetrates and invades the organoid tissue and remains present throughout the course of infection. These results demonstrate the utility of this new model to the field and highlight the potential for this system to elucidate fungal pathogenesis to develop new therapeutic strategies to prevent and treat the disseminated stages of fungal diseases such as cryptococcal meningitis.en_US
dc.publisherMultidisciplinary Digital Publishing Instituteen_US
dc.relation.isversionofhttp://dx.doi.org/10.3390/jof11070539en_US
dc.rightsCreative Commons Attributionen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en_US
dc.sourceMultidisciplinary Digital Publishing Instituteen_US
dc.titleHuman Brain Organoids: A New Model to Study Cryptococcus neoformans Neurotropismen_US
dc.typeArticleen_US
dc.identifier.citationHarding, A.T.; Gehrke, L.; Vyas, J.M.; Harding, H.B. Human Brain Organoids: A New Model to Study Cryptococcus neoformans Neurotropism. J. Fungi 2025, 11, 539.en_US
dc.contributor.departmentInstitute for Medical Engineering and Scienceen_US
dc.contributor.departmentBroad Institute of MIT and Harvarden_US
dc.relation.journalJournal of Fungien_US
dc.identifier.mitlicensePUBLISHER_CC
dc.eprint.versionFinal published versionen_US
dc.type.urihttp://purl.org/eprint/type/JournalArticleen_US
eprint.statushttp://purl.org/eprint/status/PeerRevieweden_US
dc.date.updated2025-07-25T13:09:12Z
dspace.date.submission2025-07-25T13:09:12Z
mit.journal.volume11en_US
mit.journal.issue7en_US
mit.licensePUBLISHER_CC
mit.metadata.statusAuthority Work and Publication Information Neededen_US


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