Evidence map›Paper›PMID 40801645›Full record

ArticleCells2025

Generation of Individualized, Standardized, and Electrically Synchronized Human Midbrain Organoids.

Sanae El Harane, Bahareh Nazari, Nadia El Harane, Manon Locatelli, Bochra Zidi, Stéphane Durual, Abderrahim Karmime, Florence Ravier, Adrien Roux, Luc Stoppini and 2 more

Abstract read
In one paragraph

Article in Cells, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Sanae El HaraneDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.ORCID 0000-0002-9738-7226
Bahareh NazariDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
Nadia El HaraneDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
Manon LocatelliDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
Bochra ZidiDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.
Stéphane DurualLaboratory of Biomaterials, Faculty of Dental Medicine, University of Geneva, 1206 Geneva, Switzerland.ORCID 0000-0002-9772-8406
Abderrahim KarmimeLaboratory of Toxicology and Therapeutic Drug Monitoring, Geneva University Hospitals, 1205 Geneva, Switzerland.
Florence RavierLaboratory of Toxicology and Therapeutic Drug Monitoring, Geneva University Hospitals, 1205 Geneva, Switzerland.
Adrien RouxTissue Engineering Laboratory, HEPIA HES-SO University of Applied Sciences and Arts Western Switzerland, 1202 Geneva, Switzerland.ORCID 0000-0001-7618-6129
Luc StoppiniTissue Engineering Laboratory, HEPIA HES-SO University of Applied Sciences and Arts Western Switzerland, 1202 Geneva, Switzerland.ORCID 0000-0002-2648-7051
Olivier Preynat-SeauveDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.ORCID 0000-0001-5364-967X
Karl-Heinz KrauseDepartment of Pathology and Immunology, Faculty of Medicine, University of Geneva, 1206 Geneva, Switzerland.ORCID 0000-0002-9033-6768

Funding

Clayton Foundation NA
6 · The paper itself

Abstract

Organoids allow to model healthy and diseased human tissues. and have applications in developmental biology, drug discovery, and cell therapy. Traditionally cultured in immersion/suspension, organoids face issues like lack of standardization, fusion, hypoxia-induced necrosis, continuous agitation, and high media volume requirements. To address these issues, we developed an air-liquid interface (ALi) technology for culturing organoids, termed AirLiwell. It uses non-adhesive microwells for generating and maintaining individualized organoids on an air-liquid interface. This method ensures high standardization, prevents organoid fusion, eliminates the need for agitation, simplifies media changes, reduces media volume, and is compatible with Good Manufacturing Practices. We compared the ALi method to standard immersion culture for midbrain organoids, detailing the process from human pluripotent stem cell (hPSC) culture to organoid maturation and analysis. Air-liquid interface organoids (3D-ALi) showed optimized size and shape standardization. RNA sequencing and immunostaining confirmed neural/dopaminergic specification. Single-cell RNA sequencing revealed that immersion organoids (3D-i) contained 16% fibroblast-like, 23% myeloid-like, and 61% neural cells (49% neurons), whereas 3D-ALi organoids comprised 99% neural cells (86% neurons). Functionally, 3D-ALi organoids showed a striking electrophysiological synchronization, unlike the heterogeneous activity of 3D-i organoids. This standardized organoid platform improves reproducibility and scalability, demonstrated here with midbrain organoids. The use of midbrain organoids is particularly relevant for neuroscience and neurodegenerative diseases, such as Parkinson's disease, due to their high incidence, opening new perspectives in disease modeling and cell therapy. In addition to hPSC-derived organoids, the method's versatility extends to cancer organoids and 3D cultures from primary human cells.

Indexed as

Cell Culture TechniquesMesencephalonOrganoidsCell DifferentiationHumansPluripotent Stem Cells3D cell cultureair–liquid interfaceAirLiwellcell therapyelectrical recordingsneurospheresorganoidsParkinson’s diseasepluripotent stem cellsspheroids

Identifiers

PMID40801645
PMCPMC12346388

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.