Evidence map›Paper›PMID 27677963›Full record

ArticleStem cell research & therapy2016

The effect of mesenchymal stromal cell sheets on the inflammatory stage of flexor tendon healing.

Hua Shen, Ioannis Kormpakis, Necat Havlioglu, Stephen W Linderman, Shelly E Sakiyama-Elbert, Isaac E Erickson, Thomas Zarembinski, Matthew J Silva, Richard H Gelberman, Stavros Thomopoulos

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell research & therapy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed, 1 pooled it
6.9field-weighted citation impact, top 3% 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

48 citing papers in PubMed, 1 synthesis or guideline pooled it, 92 citations in OpenAlex.

  1. Pooled it
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  7. Article
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  9. Article
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  11. Article
  12. Review
  13. Advances in mesenchymal stem cells therapy for tendinopathies.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2024
    Review
  14. Review
  15. The effects of NF-κB suppression on the early healing response following intrasynovial tendon repair in a canine model.Journal of orthopaedic research : official publication of the Orthopaedic Research Society · 2023
    Article
  16. Article
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  19. Multicellular Bioprinting of Biomimetic Inks for Tendon-to-Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023
    Article
  20. Article
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 4 institutions in 1 country.

Hua ShenDepartment of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus, Box 8233, St. Louis, MO, 63110, USA.
Ioannis KormpakisDepartment of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus, Box 8233, St. Louis, MO, 63110, USA.
Necat HavliogluDepartment of Pathology, John Cochran VA Medical Center, St. Louis, MO, USA.
Stephen W LindermanDepartment of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus, Box 8233, St. Louis, MO, 63110, USA.
Shelly E Sakiyama-ElbertDepartment of Biomedical Engineering, Washington University in St. Louis, St. Louis, MO, USA.
Isaac E EricksonBiotime, Inc., Alameda, CA, USA.
Thomas ZarembinskiBiotime, Inc., Alameda, CA, USA.
Matthew J SilvaDepartment of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus, Box 8233, St. Louis, MO, 63110, USA.
Richard H GelbermanDepartment of Orthopaedic Surgery, Washington University, 660 South Euclid, Campus, Box 8233, St. Louis, MO, 63110, USA. gelberman@wudosis.wustl.edu.
Stavros ThomopoulosDepartment of Orthopedic Surgery, Columbia University, Black Building 1408, 650 W 168 ST, New York, NY, 10032, USA. sat2@columbia.edu.
Washington University in St. Louis · USLineage Cell Therapeutics (United States) · USColumbia University · USJohn Cochran VA Medical Center · US

Funding

The Role of the Osteoblast Secretome in Bone FormationP30AR057235 · NIAMS · WASHINGTON UNIVERSITY · PI SWARNKAR, GAURAV · 2009 to 2018
$5.7M
Enhanced Tendon Healing Through Growth Factor and Cell TherapiesR01AR062947 · NIAMS · WASHINGTON UNIVERSITY · PI GELBERMAN, RICHARD H, THOMOPOULOS, STAVROS · 2012 to 2022
$5.5M
Skeletal Disorders Training ProgramT32AR060719 · NIAMS · WASHINGTON UNIVERSITY · PI Roberto Civitelli · 2011 to 2026
$4.6M
Improved orthopaedic repairs through mechanically optimized, adhesive biomaterialsF30AR069491 · NIAMS · WASHINGTON UNIVERSITY · PI LINDERMAN, STEPHEN W · 2016 to 2018
$140k
NIAMS NIH HHS F30 AR069491NIAMS NIH HHS P30 AR057235NIAMS NIH HHS R01 AR062947NIAMS NIH HHS T32 AR060719
6 · The paper itself

Abstract

backgroundThe clinical outcomes following intrasynovial flexor tendon repair are highly variable. Excessive inflammation is a principal factor underlying the formation of adhesions at the repair surface and affecting matrix regeneration at the repair center that limit tendon excursion and impair tendon healing. A previous in-vitro study revealed that adipose-derived mesenchymal stromal cells (ASCs) modulate tendon fibroblast response to macrophage-induced inflammation. The goal of the current study was therefore to explore the effectiveness of autologous ASCs on the inflammatory stage of intrasynovial tendon healing in vivo using a clinically relevant animal model.

methodsZone II flexor tendon transections and suture repairs were performed in a canine model. Autologous ASC sheets were delivered to the surface of repaired tendons. Seven days after repair, the effects of ASCs on tendon healing, with a focus on the inflammatory response, were evaluated using gene expression assays, immunostaining, and histological assessments.

resultsASCs delivered via the cell sheet infiltrated the host tendon, including the repair surface and the space between the tendon ends, as viewed histologically by tracking GFP-expressing ASCs. Gene expression results demonstrated that ASCs promoted a regenerative/anti-inflammatory M2 macrophage phenotype and regulated tendon matrix remodeling. Specifically, there were significant increases in M2-stimulator (IL-4), marker (CD163 and MRC1), and effector (VEGF) gene expression in ASC-sheet treated tendons compared with nontreated tendons. When examining changes in extracellular matrix expression, tendon injury caused a significant increase in scar-associated COL3A1 expression and reductions in COL2A1 and ACAN expression. The ASC treatment effectively counteracted these changes, returning the expression levels of these genes closer to normal. Immunostaining further confirmed that ASC treatment increased CD163

conclusionsThis study provides a novel approach for delivering ASCs with outcomes indicating potential for substantial modulation of the inflammatory environment and enhancement of tendon healing after flexor tendon repair.

Indexed as

Adipose-derived mesenchymal stromal cellsCell sheetFlexor tendonInflammationIntrasynovial tendonMacrophageTendonTissue engineering

Identifiers

PMID27677963
PMCPMC5039894
OpenAlexW2526565213

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.