Evidence map›Paper›PMID 26293548›Full record

ArticleThe Journal of thoracic and cardiovascular surgery2015

Injectable shear-thinning hydrogels used to deliver endothelial progenitor cells, enhance cell engraftment, and improve ischemic myocardium.

Ann C Gaffey, Minna H Chen, Chantel M Venkataraman, Alen Trubelja, Christopher B Rodell, Patrick V Dinh, George Hung, John W MacArthur, Renganaden V Soopan, Jason A Burdick and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of thoracic and cardiovascular surgery, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed, 1 pooled it
14.8field-weighted citation impact, top 1% 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

65 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.

  1. Pooled it
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  7. Submucosal Hydrogel for Spring-Mediated Intestinal Lengthening.Journal of biomedical materials research. Part A · 2025
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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 1 institution in 1 country.

Ann C GaffeyDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
Minna H ChenDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pa.
Chantel M VenkataramanDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
Alen TrubeljaDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
Christopher B RodellDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pa.
Patrick V DinhDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
George HungDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
John W MacArthurDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
Renganaden V SoopanDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa.
Jason A BurdickDepartment of Bioengineering, University of Pennsylvania, Philadelphia, Pa.
Pavan AtluriDivision of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania, Philadelphia, Pa. Electronic address: Pavan.atluri@uphs.upenn.edu.
University of Pennsylvania · US

Funding

Engineered Stem Cell Microenvironments for controlled VasculogenesisR01HL107938 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI GERECHT, SHARON · 2011 to 2015
$2.1M
Localized Targeting of Matrix Proteases Following Myocardial InfarctionR01HL111090 · NHLBI · UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA · PI BURDICK, JASON A, SPINALE, FRANCIS G · 2012 to 2015
$2.0M
NHLBI NIH HHS R01 HL107938NHLBI NIH HHS R01 HL111090
6 · The paper itself

Abstract

objectivesThe clinical translation of cell-based therapies for ischemic heart disease has been limited because of low cell retention (<1%) within, and poor targeting to, ischemic myocardium. To address these issues, we developed an injectable hyaluronic acid (HA) shear-thinning hydrogel (STG) and endothelial progenitor cell (EPC) construct (STG-EPC). The STG assembles as a result of interactions of adamantine- and β-cyclodextrin-modified HA. It is shear-thinning to permit delivery via a syringe, and self-heals upon injection within the ischemic myocardium. This directed therapy to the ischemic myocardial border zone enables direct cell delivery to address adverse remodeling after myocardial infarction. We hypothesize that this system will enhance vasculogenesis to improve myocardial stabilization in the context of a clinically translatable therapy.

methodsEndothelial progenitor cells (DiLDL(+) VEGFR2(+) CD34(+)) were harvested from adult male rats, cultured, and suspended in the STG. In vitro viability was quantified using a live-dead stain of EPCs. The STG-EPC constructs were injected at the border zone of ischemic rat myocardium after acute myocardial infarction (left anterior descending coronary artery ligation). The migration of the enhanced green fluorescent proteins from the construct to ischemic myocardium was analyzed using fluorescent microscopy. Vasculogenesis, myocardial remodeling, and hemodynamic function were analyzed in 4 groups: control (phosphate buffered saline injection); intramyocardial injection of EPCs alone; injection of the STG alone; and treatment with the STG-EPC construct. Hemodynamics and ventricular geometry were quantified using echocardiography and Doppler flow analysis.

resultsEndothelial progenitor cells demonstrated viability within the STG. A marked increase in EPC engraftment was observed 1-week postinjection within the treated myocardium with gel delivery, compared with EPC injection alone (17.2 ± 0.8 cells per high power field (HPF) vs 3.5 cells ± 1.3 cells per HPF, P = .0002). A statistically significant increase in vasculogenesis was noted with the STG-EPC construct (15.3 ± 5.8 vessels per HPF), compared with the control (P < .0001), EPC (P < .0001), and STG (P < .0001) groups. Statistically significant improvements in ventricular function, scar fraction, and geometry were noted after STG-EPC treatment compared with the control.

conclusionsA novel injectable shear-thinning HA hydrogel seeded with EPCs enhanced cell retention and vasculogenesis after delivery to ischemic myocardium. This therapy limited adverse myocardial remodeling while preserving contractility.

Indexed as

RegenerationTissue ScaffoldsAnimalsbeta-CyclodextrinsCell MovementCells, CulturedCell SurvivalDisease Models, AnimalEchocardiography, DopplerEndothelial Progenitor CellsFibrosisGenes, ReporterGreen Fluorescent ProteinsHyaluronic AcidHydrogelsMalebeta-Cyclodextrinsenhanced green fluorescent proteinGreen Fluorescent ProteinsHyaluronic AcidHydrogelscellular therapyhydrogelischemic myocardiumshear-thinning gel

Identifiers

PMID26293548
PMCPMC4637242
OpenAlexW2147712516

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Registered trials

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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.