Evidence map›Paper›PMID 22887987›Full record

ArticleStem cells (Dayton, Ohio)2012

Mesenchymal stem cells transmigrate between and directly through tumor necrosis factor-α-activated endothelial cells via both leukocyte-like and novel mechanisms.

Grace S L Teo, James A Ankrum, Roberta Martinelli, Sarah E Boetto, Kayla Simms, Tracey E Sciuto, Ann M Dvorak, Jeffrey M Karp, Christopher V Carman

Open access · bronzeAbstract read
In one paragraph

Article in Stem cells (Dayton, Ohio), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
101citing papers in PubMed, 2 pooled it
6.7field-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

101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 195 citations in OpenAlex.

  1. [Research progress of different types of stem cells in treatment of ischemic stroke].Zhongguo xiu fu chong jian wai ke za zhi = Zhongguo xiufu chongjian waike zazhi = Chinese journal of reparative and reconstructive surgery · 2021
    Pooled it
  2. Pooled it
  3. Engineered tumor-tropic mesenchymal stem cells as targeted therapeutic delivery systems for refractory Ovarian cancer.Journal of controlled release : official journal of the Controlled Release Society · 2026
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  7. Mesenchymal Stem Cells in Cancer Therapy.Advances in experimental medicine and biology · 2025
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41 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 4 institutions in 1 country.

Grace S L TeoDivision of Biomedical Engineering, Department of Medicine, Center for Regenerative Therapeutics, Brigham and Women's Hospital, Harvard Medical School, Harvard Stem Cell Institute, Harvard-MIT Division of Health Sciences and Technology, Cambridge, Massachusetts, USA.
James A Ankrum
Roberta Martinelli
Sarah E Boetto
Kayla Simms
Tracey E Sciuto
Ann M Dvorak
Jeffrey M Karp
Christopher V Carman
Harvard University · USBeth Israel Deaconess Medical Center · USHarvard–MIT Division of Health Sciences and Technology · USHarvard Stem Cell Institute · US

Funding

PREPARATION AND DISTRUBUTION OF ADULT STEM CELLS: HUMAN &RODENTP40RR017447 · NCRR · TULANE UNIVERSITY OF LOUISIANA · PI PROCKOP, DARWIN JOHNSON · 2003 to 2011
$8.9M
Engineered Induction of a Stem Cell Homing ResponseR01HL095722 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KARP, JEFFREY MICHAEL · 2010 to 2018
$3.9M
Mechanisms for Maintaining Endothelial Integrity During InflammationR01HL104006 · NHLBI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI CARMAN, CHRISTOPHER V · 2011 to 2014
$1.7M
Examining firm adhesion and transmigration of surface engineered MSCsR21HL097172 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI KARP, JEFFREY MICHAEL · 2010 to 2011
$470k
Characterization of endogenous stem cells within endosseous woundsR03DE019191 · NIDCR · BRIGHAM AND WOMEN'S HOSPITAL · PI KARP, JEFFREY MICHAEL · 2009 to 2010
$259k
NCRR NIH HHS P40 RR017447NCRR NIH HHS P40RR017447NHLBI NIH HHS HL095722NHLBI NIH HHS HL097172NHLBI NIH HHS HL104006NHLBI NIH HHS R01 HL095722NHLBI NIH HHS R01 HL104006NHLBI NIH HHS R21 HL097172NIDCR NIH HHS DE019191NIDCR NIH HHS R03 DE019191
6 · The paper itself

Abstract

Systemically administered adult mesenchymal stem cells (MSCs), which are being explored in clinical trials to treat inflammatory disease, exhibit the critical ability to extravasate at sites of inflammation. We aimed to characterize the basic cellular processes mediating this extravasation and compare them to those involved in leukocyte transmigration. Using high-resolution confocal and dynamic microscopy, we show that, like leukocytes, human bone marrow-derived MSC preferentially adhere to and migrate across tumor necrosis factor-α-activated endothelium in a vascular cell adhesion molecule-1 (VCAM-1) and G-protein-coupled receptor signaling-dependent manner. As several studies have suggested, we observed that a fraction of MSC was integrated into endothelium. In addition, we observed two modes of transmigration not previously observed for MSC: Paracellular (between endothelial cells) and transcellular (directly through individual endothelial cells) diapedesis through discrete gaps and pores in the endothelial monolayer, in association with VCAM-1-enriched "transmigratory cups". Contrasting leukocytes, MSC transmigration was not preceded by significant lateral migration and occurred on the time scale of hours rather than minutes. Interestingly, rather than lamellipodia and invadosomes, MSC exhibited nonapoptotic membrane blebbing activity that was similar to activities previously described for metastatic tumor and embryonic germ cells. Our studies suggest that low avidity binding between endothelium and MSC may grant a permissive environment for MSC blebbing. MSC blebbing was associated with early stages of transmigration, in which blebs could exert forces on underlying endothelial cells indicating potential functioning in breaching the endothelium. Collectively, our data suggest that MSC transmigrate actively into inflamed tissues via both leukocyte-like and novel mechanisms.

Indexed as

Transendothelial and Transepithelial MigrationAnimalsCell AdhesionCell-Derived MicroparticlesCell MembraneCells, CulturedCoculture TechniquesEndothelial CellsGTP-Binding Protein alpha Subunits, Gi-GoHumansLeukocytesMesenchymal Stem CellsMicrovesselsRatsTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1GTP-Binding Protein alpha Subunits, Gi-GoTumor Necrosis Factor-alphaVascular Cell Adhesion Molecule-1

Identifiers

PMID22887987
PMCPMC3479371
OpenAlexW2034159130

What OpenQuestion holds

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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.