Novel Co-culture Model of T Cells and Midbrain Organoids for Investigating Neurodegeneration in Parkinson's Disease

Novel Co-culture Model of T Cells and Midbrain Organoids for Investigating Neurodegeneration in Parkinson's Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Novel Co-culture Model of T Cells and Midbrain Organoids for Investigating Neurodegeneration in Parkinson's Disease iryna prots, Elizaveta Gerasimova, Amke Beenen, Daniil Kachkin, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4797877/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 28 Feb, 2025 Read the published version in npj Parkinson's Disease → Version 1 posted 10 You are reading this latest preprint version Abstract Recent studies demonstrate that brain infiltration of peripheral immune cells and their interaction with brain-resident cells contribute to Parkinson’s disease (PD) pathology. To investigate an interaction of T cells and brain-resident cells in the midbrain in spatial manner, we developed a three-dimensional (3D) human model comprising stem cell-derived human midbrain organoids (hMO) and peripheral blood T cells. We demonstrated that the complex 3D structure of organoids consists of multiple midbrain-specific cell types, allowing to study T cell motility and T cell interactions with midbrain tissue in a spatially organized microenvironment. We tested different co-culture conditions and determined optimal settings for studying T cell driven effects on hMO. T cells infiltrate hMO tissue and cause neural cell loss in hMO. Our work establishes a novel 3D cell co-culture model as a promising tool to investigate the effect of the adaptive immune system on midbrain in the context of PD. Health sciences/Diseases/Neurological disorders/Parkinson's disease Health sciences/Neurology/Neurological disorders/Parkinson's disease Biological sciences/Stem cells/Pluripotent stem cells/Induced pluripotent stem cells Biological sciences/Immunology/Neuroimmunology Biological sciences/Neuroscience/Diseases of the nervous system/Parkinson's disease Full Text Additional Declarations (Not answered) Cite Share Download PDF Status: Published Journal Publication published 28 Feb, 2025 Read the published version in npj Parkinson's Disease → Version 1 posted Editorial decision: Reject after peer review 26 Sep, 2024 Review # 3 received at journal 12 Sep, 2024 Reviewer # 3 agreed at journal 26 Aug, 2024 Review # 1 received at journal 19 Aug, 2024 Reviewer # 2 agreed at journal 16 Aug, 2024 Reviewer # 1 agreed at journal 09 Aug, 2024 Reviewers invited by journal 09 Aug, 2024 Editor assigned by journal 30 Jul, 2024 Submission checks completed at journal 29 Jul, 2024 First submitted to journal 24 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4797877","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":338012238,"identity":"9de1b9d5-504f-48e7-8f9c-0a0913a180cb","order_by":0,"name":"iryna 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