Evidence map›Paper›PMID 36959625›Full record

ArticleStem cell research & therapy2023

Human cortical spheroids with a high diversity of innately developing brain cell types.

Kim M A De Kleijn, Wieteke A Zuure, Kirsten R Straasheijm, Marijn B Martens, M Cristina Avramut, Roman I Koning, Gerard J M Martens

Open access · goldFull text read
In one paragraph

Article in Stem cell research & therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
2.2field-weighted citation impact, top 14% of its field
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

8 citing papers in PubMed, 11 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. An Overview of Multiple Sclerosis In Vitro Models.International journal of molecular sciences · 2024
    Review
  5. Article
  6. Article
  7. Blood-Brain Barrier Breakdown in Neuroinflammation: Current In Vitro Models.International journal of molecular sciences · 2023
    Review
  8. 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

7 authors at 3 institutions in 1 country.

Kim M A De KleijnDepartment of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Radboud University, 6525GA, Nijmegen, The Netherlands. k.m.a.dekleijn@amsterdamumc.nl.
Wieteke A ZuureDepartment of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Radboud University, 6525GA, Nijmegen, The Netherlands.
Kirsten R StraasheijmNeuroDrug Research Ltd, 6525ED, Nijmegen, The Netherlands.
Marijn B MartensNeuroDrug Research Ltd, 6525ED, Nijmegen, The Netherlands.
M Cristina AvramutDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands.
Roman I KoningDepartment of Cell and Chemical Biology, Leiden University Medical Center, 2300RC, Leiden, The Netherlands.
Gerard J M MartensDepartment of Molecular Animal Physiology, Donders Institute for Brain, Cognition and Behavior, Centre for Neuroscience, Faculty of Science, Radboud University, 6525GA, Nijmegen, The Netherlands.
Radboud University Nijmegen · NLLeiden University Medical Center · NLNetherlands Institute for Neuroscience · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThree-dimensional (3D) human brain spheroids are instrumental to study central nervous system (CNS) development and (dys)function. Yet, in current brain spheroid models the limited variety of cell types hampers an integrated exploration of CNS (disease) mechanisms.

methodsHere we report a 5-month culture protocol that reproducibly generates H9 embryonic stem cell-derived human cortical spheroids (hCSs) with a large cell-type variety.

resultsWe established the presence of not only neuroectoderm-derived neural progenitor populations, mature excitatory and inhibitory neurons, astrocytes and oligodendrocyte (precursor) cells, but also mesoderm-derived microglia and endothelial cell populations in the hCSs via RNA-sequencing, qPCR, immunocytochemistry and transmission electron microscopy. Transcriptomic analysis revealed resemblance between the 5-months-old hCSs and dorsal frontal rather than inferior regions of human fetal brains of 19-26 weeks of gestational age. Pro-inflammatory stimulation of the generated hCSs induced a neuroinflammatory response, offering a proof-of-principle of the applicability of the spheroids.

conclusionsOur protocol provides a 3D human brain cell model containing a wide variety of innately developing neuroectoderm- as well as mesoderm-derived cell types, furnishing a versatile platform for comprehensive examination of intercellular CNS communication and neurological disease mechanisms.

Indexed as

BrainNeuronsAstrocytesCells, CulturedHumansInfantSpheroids, CellularBrain organoidBrain spheroidEmbryonic stem cellEndothelial cellsGlial cellsMesodermNeuroectodermNeuronal cells

Identifiers

PMID36959625
PMCPMC10035191
OpenAlexW4360615199

What Socratic holds

Textfull text, public
LicenceCC BY
reference markers read5
measurements read86
Read underepoch 390

Registered trials

None linked

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 Socratic graph.