Evolving technology/basic science
Tissue-engineered, hydrogel-based endothelial progenitor cell therapy robustly revascularizes ischemic myocardium and preserves ventricular function

Read at the 94th Annual Meeting of The American Association for Thoracic Surgery, Toronto, Ontario, Canada, April 26-30, 2014.
https://doi.org/10.1016/j.jtcvs.2014.06.038Get rights and content
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Objectives

Cell-based angiogenic therapy for ischemic heart failure has had limited clinical impact, likely related to low cell retention (<1%) and dispersion. We developed a novel, tissue-engineered, hydrogel-based cell-delivery strategy to overcome these limitations and provide prolonged regional retention of myocardial endothelial progenitor cells at high cell dosage.

Methods

Endothelial progenitor cells were isolated from Wistar rats and encapsulated in fibrin gels. In vitro viability was quantified using a fluorescent live-dead stain of transgenic enhanced green fluorescent protein+ endothelial progenitor cells. Endothelial progenitor cell-laden constructs were implanted onto ischemic rat myocardium in a model of acute myocardial infarction (left anterior descending ligation) for 4 weeks. Intramyocardial cell injection (2 × 106 endothelial progenitor cells), empty fibrin, and isolated left anterior descending ligation groups served as controls. Hemodynamics were quantified using echocardiography, Doppler flow analysis, and intraventricular pressure-volume analysis. Vasculogenesis and ventricular geometry were quantified. Endothelial progenitor cell migration was analyzed by using endothelial progenitor cells from transgenic enhanced green fluorescent protein+ rodents.

Results

Endothelial progenitor cells demonstrated an overall 88.7% viability for all matrix and cell conditions investigated after 48 hours. Histologic assessment of 1-week implants demonstrated significant migration of transgenic enhanced green fluorescent protein+ endothelial progenitor cells from the fibrin matrix to the infarcted myocardium compared with intramyocardial cell injection (28 ± 12.3 cells/high power field vs 2.4 ± 2.1 cells/high power field, P = .0001). We also observed a marked increase in vasculogenesis at the implant site. Significant improvements in ventricular hemodynamics and geometry were present after endothelial progenitor cell-hydrogel therapy compared with control.

Conclusions

We present a tissue-engineered, hydrogel-based endothelial progenitor cell-mediated therapy to enhance cell delivery, cell retention, vasculogenesis, and preservation of myocardial structure and function.

CTSNet classification

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Abbreviations and Acronyms

DAPI
4′,6-diamidino-2-phenylindole
eGFP
enhanced green fluorescent protein
EPC
endothelial progenitor cell
FITC
fluorescein isothiocyanate
hpf
high power field
LAD
left anterior descending
PBS
phosphate-buffered saline
SMA
smooth muscle actin

Cited by (0)

This project was supported by the National Institutes of Health, National Heart, Lung, Blood Institute Grant 1RO1 HL089315 (to Y.J.W.); the American Association for Thoracic Surgery, David C. Sabiston Research Scholarship (to P.A.); and the American Heart Association, Scientist Development Grant 13SDG17230005 (to P.A.)

Disclosures: Authors have nothing to disclose with regard to commercial support.