ArticleNature methods2023
In vitro modeling of the human dopaminergic system using spatially arranged ventral midbrain-striatum-cortex assembloids.
Article in Nature methods, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 88 citations in OpenAlex.
- Organoids: Key advances, optimization, and technological iterations in their application to neurodegenerative diseases.Neural regeneration research · 2026Article
- Engineering functional ventral midbrain dopaminergic neurons in human organoids through WNT modulation and bioreactor culture.Molecular psychiatry · 2026Article
- Brain organoids as models of extracellular vesicle-mediated human neural communication.Neural regeneration research · 2026Article
- Cerebral organoids as a platform to model prenatal exposure to drugs of abuse.Neural regeneration research · 2026Article
- Stem cell derived neural organoid approaches for neurological diseases.Neural regeneration research · 2026Article
- Micro- and nanoplastics alter electrophysiological brain patterns and reshape human neurodevelopmental trajectories.bioRxiv : the preprint server for biology · 2026Article
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
- Using Brain Organoids to Explore Human Neurobiology.Cellular and molecular neurobiology · 2026Review
- Beyond phenotypic markers: rethinking dopaminergic identity in iPSC-derived neurons.Cell communication and signaling : CCS · 2026Review
- Advances and applications of brain organoids in central nervous system disorders: Bridging the gap from laboratory to clinic.Neural regeneration research · 2026Article
- Modeling striatal development and disease with human pluripotent stem cells.Inflammation and regeneration · 2026Review
- Next-Generation Strategies for Neural Repair and Regeneration: Neural Organoid Transplantation in the CNS.Cell proliferation · 2026Review
- Spatially defined axonal guidance in neural organoids with micropatterned microfluidic channels.bioRxiv : the preprint server for biology · 2026Article
- Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- A multicellular analysis calcium imaging toolbox for ImageJ.Cell reports methods · 2026Article
- Single-cell transcriptomics revealed molecular vulnerability in a human midbrain-like organoid model of Parkinson's disease.iScience · 2026Article
- Parabiosis, Assembloids, Organoids (PAO).Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Generating and characterizing human telencephalic brain organoids from stem cell-derived single neural rosettes.Nature protocols · 2026Review
- Stem Cell Models for Elucidating Cellular Mechanisms of Substance Use Disorders and Advancing Addiction Pharmacology.Stem cells international · 2026Review
- Differentiation of human iPSCs into dopaminergic neurons: comparative analysis of 2D and 3D protocols for disease modeling and pharmacology.Neuroscience applied · 2026Review
8 more citing papers are in PubMed but not listed here.
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Authors and funding
18 authors at 6 institutions in 7 countries.
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Abstract
Ventral midbrain dopaminergic neurons project to the striatum as well as the cortex and are involved in movement control and reward-related cognition. In Parkinson's disease, nigrostriatal midbrain dopaminergic neurons degenerate and cause typical Parkinson's disease motor-related impairments, while the dysfunction of mesocorticolimbic midbrain dopaminergic neurons is implicated in addiction and neuropsychiatric disorders. Study of the development and selective neurodegeneration of the human dopaminergic system, however, has been limited due to the lack of an appropriate model and access to human material. Here, we have developed a human in vitro model that recapitulates key aspects of dopaminergic innervation of the striatum and cortex. These spatially arranged ventral midbrain-striatum-cortical organoids (MISCOs) can be used to study dopaminergic neuron maturation, innervation and function with implications for cell therapy and addiction research. We detail protocols for growing ventral midbrain, striatal and cortical organoids and describe how they fuse in a linear manner when placed in custom embedding molds. We report the formation of functional long-range dopaminergic connections to striatal and cortical tissues in MISCOs, and show that injected, ventral midbrain-patterned progenitors can mature and innervate the tissue. Using these assembloids, we examine dopaminergic circuit perturbations and show that chronic cocaine treatment causes long-lasting morphological, functional and transcriptional changes that persist upon drug withdrawal. Thus, our method opens new avenues to investigate human dopaminergic cell transplantation and circuitry reconstruction as well as the effect of drugs on the human dopaminergic system.
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