Evidence map›Paper›PMID 34021557›Full record

ArticleLab on a chip2021

Tubular human brain organoids to model microglia-mediated neuroinflammation.

Zheng Ao, Hongwei Cai, Zhuhao Wu, Sunghwa Song, Hande Karahan, Byungwook Kim, Hui-Chen Lu, Jungsu Kim, Ken Mackie, Feng Guo

Open access · greenAbstract read
In one paragraph

Article in Lab on a chip, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 2 pooled it
6.3field-weighted citation impact, top 2% 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

55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 83 citations in OpenAlex.

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  14. A Comprehensive Review on Utilizing Human Brain Organoids to Study Neuroinflammation in Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025
    Review
  15. Human brain organoids for understanding substance use disorders.Drug metabolism and pharmacokinetics · 2025
    Review
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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

10 authors at 2 institutions in 2 countries.

Zheng AoDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, USA. fengguo@iu.edu.
Hongwei CaiDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, USA. fengguo@iu.edu.
Zhuhao WuDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, USA. fengguo@iu.edu.
Sunghwa SongDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, USA. fengguo@iu.edu.
Hande KarahanStark Neurosciences Research Institute, and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.ORCID http://orcid.org/0000-0003-3192-7362
Byungwook KimStark Neurosciences Research Institute, and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.ORCID http://orcid.org/0000-0001-8390-7713
Hui-Chen LuGill Center for Biomolecular Science, and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.
Jungsu KimStark Neurosciences Research Institute, and Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202, USA.ORCID http://orcid.org/0000-0002-6931-8581
Ken MackieGill Center for Biomolecular Science, and Department of Psychological and Brain Sciences, Indiana University, Bloomington, IN 47405, USA.ORCID http://orcid.org/0000-0001-8501-6199
Feng GuoDepartment of Intelligent Systems Engineering, Indiana University, Bloomington, IN 47405, USA. fengguo@iu.edu.ORCID http://orcid.org/0000-0001-9103-3235
Bloomington Health Foundation · USNeurosciences Institute · US

Funding

CB2 Cannabinoid Mechanisms for Suppressing Opioid Tolerance and DependenceR01DA047858 · NIDA · TRUSTEES OF INDIANA UNIVERSITY · PI HOHMANN, ANDREA GRACE, MACKIE, KENNETH · 2019 to 2023
$2.6M
An acoustofluidic avidity cytometer for massive parallel profiling single autoreactive T cell in autoimmune diseaseDP2AI160242 · NIAID · TRUSTEES OF INDIANA UNIVERSITY · PI GUO, FENG · 2020 to 2020
$2.4M
Acquisition of a DeltaVision OMX-SR Imaging SystemS10OD024988 · OD · INDIANA UNIVERSITY INDIANAPOLIS · PI WALCZAK, CLAIRE E · 2018 to 2018
$600k
Acoustic assembly of patient tumor organoids for modeling cancer immunityR03EB030331 · NIBIB · TRUSTEES OF INDIANA UNIVERSITY · PI GUO, FENG · 2020 to 2021
$159k
NIAID NIH HHS DP2 AI160242NIBIB NIH HHS R03 EB030331NIDA NIH HHS R01 DA047858NIH HHS S10 OD024988
6 · The paper itself

Abstract

Human brain organoids, 3D brain tissue cultures derived from human pluripotent stem cells, hold promising potential in modeling neuroinflammation for a variety of neurological diseases. However, challenges remain in generating standardized human brain organoids that can recapitulate key physiological features of a human brain. Here, we present tubular organoid-on-a-chip devices to generate better organoids and model neuroinflammation. By employing 3D printed hollow mesh scaffolds, our device can be easily incorporated into multiwell-plates for reliable, scalable, and reproducible generation of tubular organoids. By introducing rocking flows through the tubular device channel, our device can perfuse nutrients and oxygen to minimize organoid necrosis and hypoxia, and incorporate immune cells into organoids to model neuro-immune interactions. Compared with conventional protocols, our method increased neural progenitor proliferation and reduced heterogeneity of human brain organoids. As a proof-of-concept application, we applied this method to model the microglia-mediated neuroinflammation after exposure to an opioid receptor agonist. We found isogenic microglia were activated after exposure to an opioid receptor agonist (DAMGO) and transformed back to the homeostatic status with further treatment by a cannabinoid receptor 2 (CB2) agonist (LY2828360). Importantly, the activated microglia in tubular organoids had stronger cytokine responses compared to those in 2D microglial cultures. Our tubular organoid device is simple, versatile, inexpensive, easy-to-use, and compatible with multiwell-plates, so it can be widely used in common research and clinical laboratory settings. This technology can be broadly used for basic and translational applications in inflammatory diseases including substance use disorders, neural diseases, autoimmune disorders, and infectious diseases.

Indexed as

Induced Pluripotent Stem CellsPluripotent Stem CellsBrainHumansMicrogliaOrganoids

Identifiers

PMID34021557
PMCPMC8493632
OpenAlexW3161619369

What OpenQuestion holds

Textmetadata
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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.