Evidence map›Paper›PMID 38365833›Full record

ArticleJournal of neuroinflammation2024

Advanced patient-specific microglia cell models for pre-clinical studies in Alzheimer's disease.

Carla Cuní-López, Romal Stewart, Lotta E Oikari, Tam Hong Nguyen, Tara L Roberts, Yifan Sun, Christine C Guo, Michelle K Lupton, Anthony R White, Hazel Quek

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Journal of neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed, 1 pooled it
4.9field-weighted citation impact, top 4% 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

16 citing papers in PubMed, 1 synthesis or guideline pooled it, 20 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Article
  8. Loss of Nuclear TDP-43 Impairs Lipid Metabolism in Microglia-Like Cells.bioRxiv : the preprint server for biology · 2025
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  13. AssessingFrontiers in immunology · 2025
    Review
  14. CD33 and SHP-1/Genes · 2024
    Article
  15. Article
  16. Tackling neurodegenerationFrontiers in molecular neuroscience · 2024
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 4 institutions in 1 country.

Carla Cuní-LópezMental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Romal StewartMental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Lotta E OikariMental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Tam Hong NguyenScientific Services, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Tara L RobertsUQ Centre for Clinical Research, The University of Queensland, Brisbane City, QLD, 4029, Australia.
Yifan SunMental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Christine C GuoMental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Michelle K LuptonMental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia.
Anthony R White *Mental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia. Tony.White@qimrberghofer.edu.au.
Hazel Quek *Mental Health and Neuroscience Department, QIMR Berghofer Medical Research Institute, Herston, QLD, 4006, Australia. Hazel.Quek@qimrberghofer.edu.au.
QIMR Berghofer Medical Research Institute · AUUniversity of Queensland · AUIngham Institute · AUQueensland University of Technology · AU

Funding

National Health and Medical Research Council APP1095227National Health and Medical Research Council of Australia APP1125796NHMRC Boosting Dementia Leadership Fellowship APP1140441NHMRC Senior Research Fellowship APP1118452
6 · The paper itself

Abstract

backgroundAlzheimer's disease (AD) is an incurable neurodegenerative disorder with a rapidly increasing prevalence worldwide. Current approaches targeting hallmark pathological features of AD have had no consistent clinical benefit. Neuroinflammation is a major contributor to neurodegeneration and hence, microglia, the brain's resident immune cells, are an attractive target for potentially more effective therapeutic strategies. However, there is no current in vitro model system that captures AD patient-specific microglial characteristics using physiologically relevant and experimentally flexible culture conditions.

methodsTo address this shortcoming, we developed novel 3D Matrigel-based monocyte-derived microglia-like cell (MDMi) mono-cultures and co-cultures with neuro-glial cells (ReNcell VM). We used single-cell RNA sequencing (scRNAseq) analysis to compare the transcriptomic signatures of MDMi between model systems (2D, 3D and 3D co-culture) and against published human microglia datasets. To demonstrate the potential of MDMi for use in personalized pre-clinical strategies, we generated and characterized MDMi models from sixteen AD patients and matched healthy controls, and profiled cytokine responses upon treatment with anti-inflammatory drugs (dasatinib and spiperone).

resultsMDMi in 3D exhibited a more branched morphology and longer survival in culture compared to 2D. scRNAseq uncovered distinct MDMi subpopulations that exhibit higher functional heterogeneity and best resemble human microglia in 3D co-culture. AD MDMi in 3D co-culture showed altered cell-to-cell interactions, growth factor and cytokine secretion profiles and responses to amyloid-β. Drug testing assays revealed patient- and model-specific cytokine responses.

conclusionOur study presents a novel, physiologically relevant and AD patient-specific 3D microglia cell model that opens avenues towards improving personalized drug development strategies in AD.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesCytokinesHumansMicrogliaNeurogliaAmyloid beta-PeptidesCytokines3D cell modelingAlzheimer’s diseaseDrugsMicrogliaMonocytesPatient

Identifiers

PMID38365833
PMCPMC10870454
OpenAlexW4391879623

What OpenQuestion holds

Textmetadata
LicenceCC BY
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 OpenQuestion graph.