Evidence map›Paper›PMID 21836091›Full record

ArticleStroke2011

The CCR2/CCL2 interaction mediates the transendothelial recruitment of intravascularly delivered neural stem cells to the ischemic brain.

Robert H Andres, Raymond Choi, Arjun V Pendharkar, Xavier Gaeta, Nancy Wang, Jaya K Nathan, Joshua Y Chua, Star W Lee, Theo D Palmer, Gary K Steinberg and 1 more

Abstract read
In one paragraph

Article in Stroke, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.

0numbers the graph read from it
0cells of the map it votes in
72citing papers in PubMed
7.9field-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

72 citing papers in PubMed, 109 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Tracing Inflammation in Ischemic Stroke: Biomarkers and Clinical Insight.International journal of molecular sciences · 2025
    Review
  5. Review
  6. Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. The Role of Stem Cells in the Therapy of Stroke.Current neuropharmacology · 2022
    Review
  17. Article
  18. Treatment of ischemic stroke with modified mesenchymal stem cells.International journal of medical sciences · 2022
    Review
  19. Review
  20. Article

12 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

11 authors at 1 institution in 1 country.

Robert H AndresDepartment of Neurosurgery, Stanford Stroke Center, Stanford University, School of Medicine, 300 Pasteur Drive R211, Stanford, CA 94305-5327, USA.
Raymond Choi
Arjun V Pendharkar
Xavier Gaeta
Nancy Wang
Jaya K Nathan
Joshua Y Chua
Star W Lee
Theo D Palmer
Gary K Steinberg
Raphael Guzman
Stanford Medicine · US

Funding

Transgenic animal injury paradigmsP01NS037520 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 1999 to 2008
$10.8M
NMDA ANTAGONISTS IN THE TREATMENT OF STROKER01NS027292 · NINDS · STANFORD UNIVERSITY · PI STEINBERG, GARY K · 1991 to 2009
$3.7M
Stanford Neurosurgery Resident Research Education ProgramR25NS065741 · NINDS · STANFORD UNIVERSITY · PI HAYDEN GEPHART, MELANIE, STEINBERG, GARY K · 2009 to 2022
$2.0M
NINDS NIH HHS P01 NS037520NINDS NIH HHS P01 NS37520NINDS NIH HHS R01 NS027292NINDS NIH HHS R01 NS27292NINDS NIH HHS R25 NS065741
6 · The paper itself

Abstract

background and purposeThe inflammatory response is a critical component of ischemic stroke. In addition to its physiological role, the mechanisms behind transendothelial recruitment of immune cells also offer a unique therapeutic opportunity for translational stem cell therapies. Recent reports have demonstrated homing of neural stem cells (NSC) into the injured brain areas after intravascular delivery. However, the mechanisms underlying the process of transendothelial recruitment remain largely unknown. Here we describe the critical role of the chemokine CCL2 and its receptor CCR2 in targeted homing of NSC after ischemia.

methodsTwenty-four hours after induction of stroke using the hypoxia-ischemia model in mice CCR2+/+ and CCR2-/- reporter NSC were intra-arterially delivered. Histology and bioluminescence imaging were used to investigate NSC homing to the ischemic brain. Functional outcome was assessed with the horizontal ladder test.

resultsUsing NSC isolated from CCR2+/+ and CCR2-/- mice, we show that receptor deficiency significantly impaired transendothelial diapedesis specifically in response to CCL2. Accordingly, wild-type NSC injected into CCL2-/- mice exhibited significantly decreased homing. Bioluminescence imaging showed robust recruitment of CCR2+/+ cells within 6 hours after transplantation in contrast to CCR2-/- cells. Mice receiving CCR2+/+ grafts after ischemic injury showed a significantly improved recovery of neurological deficits as compared to animals with transplantation of CCR2-/- NSC.

conclusionsThe CCL2/CCR2 interaction is critical for transendothelial recruitment of intravascularly delivered NSC in response to ischemic injury. This finding could have significant implications in advancing minimally invasive intravascular therapeutics for regenerative medicine or cell-based drug delivery systems for central nervous system diseases.

Indexed as

AnimalsBrainBrain IschemiaCell DifferentiationCell ProliferationChemokine CCL2MaleMiceMice, KnockoutNeural Stem CellsReceptors, CCR2Recovery of FunctionRegenerative MedicineCcl2 protein, mouseCcr2 protein, mouseChemokine CCL2Receptors, CCR2

Identifiers

PMID21836091
PMCPMC3371396
OpenAlexW2018685391

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.