Functional consequences of a tissue-engineered myocardial patch for cardiac repair in a rat infarct model

Jacqueline S. Wendel, Lei Ye, Pengyuan Zhang, Robert T. Tranquillo, Jianyi Jay Zhang

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Cell therapies have emerged as a promising treatment for the prevention of heart failure after myocardial infarction (MI). This study evaluated the capacity of an aligned, fibrin-based, stretch-conditioned cardiac patch consisting of either the native population or a cardiomyocyte (CM)-depleted population (i.e., CM+ or CM- patches) of neonatal rat heart cells to ameliorate left ventricular (LV) remodeling in the acute-phase postinfarction in syngeneic, immunocompetent rats. Patches were exposed to 7 days of static culture and 7 days of cyclic stretching prior to implantation. Within 1 week of implantation, both patches became vascularized, and non-CMs began migrating from CM+ patches. By week 4, patches had been remodeled into collagenous tissue, and live, elongated, donor CMs were found within grafted CM+ patches. Significant improvement in cardiac contractile function was seen with the administration of the CM+ patch (ejection fraction increased from 35.1%±4.0% for MI only to 58.8%±7.3% with a CM+ patch, p<0.05) associated with a 77% reduction in infarct size (61.3%±7.9% for MI only, 13.9%±10.8% for CM+ patch, p<0.05), and the elimination of LV free-wall thinning. Decreased infarct size and reduced wall thinning also occurred with the administration of the CM- patch (infarct size 36.9%±10.2%, LV wall thickness: 1058.2±135.4μm for CM- patch, 661.3±37.4μm for MI only, p<0.05), but without improvements in cardiac function. Approximately 36.5% of the transplanted CMs survived at 4 weeks; however, they remained separated and electrically uncoupled from the host myocardium by a layer of CM-free tissue, which suggests that the benefits of CM+ patch transplantation resulted from paracrine mechanisms originating from CMs. Collectively, these observations suggest that the transplantation of CM-containing engineered heart tissue patches can lead to dramatic improvements in cardiac function and remodeling after acute MI.

Original languageEnglish (US)
Pages (from-to)1325-1335
Number of pages11
JournalTissue Engineering - Part A
Volume20
Issue number7-8
DOIs
StatePublished - Apr 1 2014

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Cardiac Myocytes
Rats
Repair
Tissue
Fibrin
Stretching
Myocardial Infarction
Transplantation
Ventricular Remodeling
Cell- and Tissue-Based Therapy
Population
Myocardium
Heart Failure

Cite this

Functional consequences of a tissue-engineered myocardial patch for cardiac repair in a rat infarct model. / Wendel, Jacqueline S.; Ye, Lei; Zhang, Pengyuan; Tranquillo, Robert T.; Zhang, Jianyi Jay.

In: Tissue Engineering - Part A, Vol. 20, No. 7-8, 01.04.2014, p. 1325-1335.

Research output: Contribution to journalArticle

Wendel, Jacqueline S. ; Ye, Lei ; Zhang, Pengyuan ; Tranquillo, Robert T. ; Zhang, Jianyi Jay. / Functional consequences of a tissue-engineered myocardial patch for cardiac repair in a rat infarct model. In: Tissue Engineering - Part A. 2014 ; Vol. 20, No. 7-8. pp. 1325-1335.
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