Novel co-culture model of T cells and midbrain organoids for investigating neurodegeneration in Parkinson’s disease

Abstract Recent studies demonstrate that brain infiltration of peripheral immune cells and their interaction with brain-resident cells contribute to Parkinson’s disease (PD). However, mechanisms of T cell-brain cell communication are not fully elucidated and models allowing investigation of interact...

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Main Authors: Elizaveta Gerasimova, Amke C. Beenen, Daniil Kachkin, Martin Regensburger, Sebastian Zundler, David B. Blumenthal, Gloria Lutzny-Geier, Beate Winner, Iryna Prots
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:npj Parkinson's Disease
Online Access:https://doi.org/10.1038/s41531-025-00882-8
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Summary:Abstract Recent studies demonstrate that brain infiltration of peripheral immune cells and their interaction with brain-resident cells contribute to Parkinson’s disease (PD). However, mechanisms of T cell-brain cell communication are not fully elucidated and models allowing investigation of interaction between T cells and brain-resident cells are required. In this study, we developed a three-dimensional (3D) model composed of stem cell-derived human midbrain organoids (hMO) and peripheral blood T cells. We demonstrated that organoids consist of multiple midbrain-specific cell types, allowing to study T cell motility and interactions with midbrain tissue in a spatially organized microenvironment. We optimized co-culture conditions and demonstrated that T cells infiltrate hMO tissue, leading to neural cell loss. Our work establishes a novel 3D cell co-culture model as a promising tool to investigate the effect of the adaptive immune system on the midbrain and can be used in future studies to address these processes in the context of PD.
ISSN:2373-8057