Air-Liquid interface midbrain organoids model the pathological features of Parkinson's disease.
Air-Liquid interface midbrain organoids model the pathological features of Parkinson's disease.
Where did the research take place?
The study site has not been established. Author addresses may differ from where the research occurred.
Kuopio, FI · Author affiliation
A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, 70210 Kuopio, Finland.Location evidence
Helsinki, FI · Author affiliation
Neuroscience Center, HiLIFE, and Drug Research Program, Division of Pharmacology and Pharmacotherapy, University of Helsinki 00014 Helsinki, Finland.Location evidence
Turku, FI · Author affiliation
Department of Pathology, Turku University Hospital and Institute of Biomedicine, University of Turku, Turku, Finland.Location evidence
Philadelphia, US · Author affiliation
Center for Neurodegenerative Disease Research, Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.Location evidence
A plain-language reading has not been prepared for this paper yet.
Original abstract
Human-induced pluripotent stem cell-derived midbrain organoids offer a promising platform for modeling Parkinson's disease (PD). Yet, their utility has been limited by the absence of microglia and the development of a necrotic core during maturation. Here, we present an air-liquid interface (ALI) slice culture system for extended cultivation of midbrain organoids (mORGs), enabling efficient microglial integration, improved neuronal viability, and enhanced functional maturation. Compared with conventional mORGs grown in suspension cultures, the ALI method supports more consistent engraftment of microglial progenitors and the development of astrocytes and oligodendrocyte progenitors, as revealed by single-cell RNA sequencing. Functionally, ALI-mORGs exhibited robust and reproducible neural network activity, with N-methyl-D-aspartate (NMDA) stimulation reliably inducing synchronous bursting, as measured by 3D microelectrode array recordings. Importantly, exposure to alpha-synuclein (αSyn) preformed fibrils triggered the progressive accumulation of phosphorylated αSyn inclusions, closely recapitulating key features of PD pathology. The ALI-mORG model addresses major limitations of existing systems and provides a more physiologically relevant platform for investigating cellular mechanisms of PD and for supporting future therapeutic strategies.