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Advances, challenges, and opportunities of human midbrain organoids for modelling of the dopaminergic system

Fiorenzano, Alessandro LU ; Sozzi, Edoardo LU orcid ; Kastli, Rahel ; Iazzetta, Maria Roberta ; Bruzelius, Andreas LU ; Arlotta, Paola and Parmar, Malin LU orcid (2025) In EMBO Journal 44(15). p.4181-4195
Abstract

Dopaminergic neurons in the ventral midbrain are critical for regulating movement, cognition, and emotion. Ventral midbrain organoids can be used to model both development and diseases of the dopaminergic system, especially Parkinson’s disease. Here, we summarize recent advances and remaining challenges in developing such three-dimensional organoids from human pluripotent stem cells. We outline how ventral midbrain organoid systems have progressed from early three-dimensional culture models to sophisticated, engineered, multiregional systems that more accurately replicate the complex network of dopaminergic neurons. Furthermore, we examine how the development of organoid models from other brain regions, particularly the forebrain,... (More)

Dopaminergic neurons in the ventral midbrain are critical for regulating movement, cognition, and emotion. Ventral midbrain organoids can be used to model both development and diseases of the dopaminergic system, especially Parkinson’s disease. Here, we summarize recent advances and remaining challenges in developing such three-dimensional organoids from human pluripotent stem cells. We outline how ventral midbrain organoid systems have progressed from early three-dimensional culture models to sophisticated, engineered, multiregional systems that more accurately replicate the complex network of dopaminergic neurons. Furthermore, we examine how the development of organoid models from other brain regions, particularly the forebrain, provides complementary insights that can accelerate progress also in the field of midbrain organoids, towards the generation of more advanced in vitro systems for midbrain dopaminergic neurons and their circuitry. Such cutting-edge human stem cell-based models offer powerful platforms for investigating dopaminergic neuron generation, function, and connectivity, thereby enhancing disease modelling, drug discovery, and the development of targeted cell-based therapies.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Disease Modeling, Dopaminergic Neurons, Human Pluripotent Stem Cells, Midbrain Development, Single-cell Sequencing
in
EMBO Journal
volume
44
issue
15
pages
15 pages
publisher
Oxford University Press
external identifiers
  • pmid:40604323
  • scopus:105009545643
ISSN
0261-4189
DOI
10.1038/s44318-025-00494-1
language
English
LU publication?
yes
additional info
Publisher Copyright: © The Author(s) 2025.
id
ccba42f7-a394-401a-9f7c-b11caed09b55
date added to LUP
2025-12-01 13:59:44
date last changed
2026-01-13 02:08:03
@article{ccba42f7-a394-401a-9f7c-b11caed09b55,
  abstract     = {{<p>Dopaminergic neurons in the ventral midbrain are critical for regulating movement, cognition, and emotion. Ventral midbrain organoids can be used to model both development and diseases of the dopaminergic system, especially Parkinson’s disease. Here, we summarize recent advances and remaining challenges in developing such three-dimensional organoids from human pluripotent stem cells. We outline how ventral midbrain organoid systems have progressed from early three-dimensional culture models to sophisticated, engineered, multiregional systems that more accurately replicate the complex network of dopaminergic neurons. Furthermore, we examine how the development of organoid models from other brain regions, particularly the forebrain, provides complementary insights that can accelerate progress also in the field of midbrain organoids, towards the generation of more advanced in vitro systems for midbrain dopaminergic neurons and their circuitry. Such cutting-edge human stem cell-based models offer powerful platforms for investigating dopaminergic neuron generation, function, and connectivity, thereby enhancing disease modelling, drug discovery, and the development of targeted cell-based therapies.</p>}},
  author       = {{Fiorenzano, Alessandro and Sozzi, Edoardo and Kastli, Rahel and Iazzetta, Maria Roberta and Bruzelius, Andreas and Arlotta, Paola and Parmar, Malin}},
  issn         = {{0261-4189}},
  keywords     = {{Disease Modeling; Dopaminergic Neurons; Human Pluripotent Stem Cells; Midbrain Development; Single-cell Sequencing}},
  language     = {{eng}},
  month        = {{08}},
  number       = {{15}},
  pages        = {{4181--4195}},
  publisher    = {{Oxford University Press}},
  series       = {{EMBO Journal}},
  title        = {{Advances, challenges, and opportunities of human midbrain organoids for modelling of the dopaminergic system}},
  url          = {{http://dx.doi.org/10.1038/s44318-025-00494-1}},
  doi          = {{10.1038/s44318-025-00494-1}},
  volume       = {{44}},
  year         = {{2025}},
}