Evidence map›Paper›PMID 34385693›Full record

ArticleNature biomedical engineering2021

A neurovascular-unit-on-a-chip for the evaluation of the restorative potential of stem cell therapies for ischaemic stroke.

Zhonglin Lyu, Jon Park, Kwang-Min Kim, Hye-Jin Jin, Haodi Wu, Jayakumar Rajadas, Deok-Ho Kim, Gary K Steinberg, Wonjae Lee

Open access · greenAbstract read
In one paragraph

Article in Nature biomedical engineering, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
85citing papers in PubMed, 2 pooled it
7.8field-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

85 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Article
  4. Animal stroke models and outcome evaluation: A review.Animal models and experimental medicine · 2026
    Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. An integrated investigation of systemic and localized pathophysiological mechanisms of stroke and multimodal therapeutic strategies.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026
    Review
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. HumanBioactive materials · 2026
    Article
  17. Piezo1 induces Wnt7bTheranostics · 2026
    Article
  18. Article
  19. Review
  20. Review

25 more citing papers are in PubMed but not listed here.

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

9 authors at 3 institutions in 1 country.

Zhonglin Lyu *Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0003-3229-8596
Jon Park *Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Kwang-Min Kim *Department of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Hye-Jin JinDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.
Haodi WuDepartment of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Jayakumar RajadasDepartment of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
Deok-Ho KimDepartment of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0002-6989-6074
Gary K SteinbergDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0001-6374-1058
Wonjae LeeDepartment of Neurosurgery, Stanford University School of Medicine, Stanford, CA, USA. lee.wonj@gmail.com.ORCID http://orcid.org/0000-0003-1524-2259
Stanford University · USStanford Medicine · USJohns Hopkins University · US

Funding

Stanford Center for Clinical & Translational Education and Research (Spectrum)UL1TR003142 · NCATS · STANFORD UNIVERSITY · PI O'HARA, RUTH M · 2019 to 2023
$45.0M
Spectrum Stanford Center for clinical and Translational Research and EducationUL1TR001085 · NCATS · STANFORD UNIVERSITY · PI CULLEN, MARK RICHARD, GREENBERG, HARRY BERNARD · 2013 to 2017
$37.1M
Paracrine and synaptic mechanisms underlying recovery using human stem cell theraR01NS058784 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 2008 to 2023
$6.6M
Development of microfluidic blood-brain tumor barrier model to screen chemotherapeutic strategies for breast cancer brain metastasesK25CA201545 · NCI · STANFORD UNIVERSITY · PI LEE, WONJAE · 2017 to 2021
$786k
NCATS NIH HHS UL1 TR001085NCATS NIH HHS UL1 TR003142NCI NIH HHS K25 CA201545NINDS NIH HHS R01 NS058784
6 · The paper itself

Abstract

The therapeutic efficacy of stem cells transplanted into an ischaemic brain depends primarily on the responses of the neurovascular unit. Here, we report the development and applicability of a functional neurovascular unit on a microfluidic chip as a microphysiological model of ischaemic stroke that recapitulates the function of the blood-brain barrier as well as interactions between therapeutic stem cells and host cells (human brain microvascular endothelial cells, pericytes, astrocytes, microglia and neurons). We used the model to track the infiltration of a number of candidate stem cells and to characterize the expression levels of genes associated with post-stroke pathologies. We observed that each type of stem cell showed unique neurorestorative effects, primarily by supporting endogenous recovery rather than through direct cell replacement, and that the recovery of synaptic activities is correlated with the recovery of the structural and functional integrity of the neurovascular unit rather than with the regeneration of neurons.

Indexed as

Lab-On-A-Chip DevicesStem Cell TransplantationAstrocytesBlood-Brain BarrierCoculture TechniquesEndothelial CellsHumansIschemic StrokeMicrogliaMicrovesselsModels, BiologicalNeuronsPericytesStem Cells

Identifiers

PMID34385693
PMCPMC8524779
OpenAlexW3190365857

What OpenQuestion holds

Textmetadata
LicenceTDM
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.