Tissue-engineered cardiac patches enriched with IGF1 modified mRNA alleviate myocardial infarction by enhancing cell survival and angiogenesis

TL;DR

This study shows that cardiac patches enriched with IGF1-modified mRNA improve heart repair by boosting cell survival and blood vessel growth after a heart attack.

Contribution

The novel use of IGF1-modified mRNA in tissue-engineered cardiac patches enhances cell survival and angiogenesis for myocardial repair.

Findings

TECPs with modIGF1 reduced infarct size and improved cardiac function.

ModIGF1 enhanced cell survival, proliferation, and vascularization in the heart tissue.

Nanofibrous membranes with 30% gelatin best supported cell adhesion and differentiation.

Abstract

Tissue-engineered cardiac patches (TECPs), which combine cells with biomaterial scaffolds, hold great promise for myocardial repair and regeneration. However, their broader application remains limited by the low survival rate of transplanted cells. To boost the therapeutic efficacy of cardiac patches, genetic engineering and localized delivery of bioactive factors are essential for optimizing cellular function in vivo. In this study, nanofibrous membranes composed of polycaprolactone-co-l-lactide (PLCL) and gelatin at various ratios were fabricated using electrospinning technology. Among these, membranes containing 30 % gelatin displayed optimal properties, promoting the adhesion, survival, proliferation, and cardiomyocyte differentiation of induced pluripotent stem cell-derived cardiac progenitor cells (iPSC-CPCs). Following this, TECPs were constructed in vitro and transfected with modified mRNA (modRNA) encoding insulin-like growth factor 1 (IGF1). Further evaluations revealed that IGF1 modified mRNA (modIGF1)-enriched TECPs significantly reduced infarct size, enhanced the survival and proliferation of transplanted cells, promoted vascularization and facilitated cardiac functional recovery. The integration of modRNA technology with myocardial patches facilitates the controlled release of therapeutic proteins, thereby preserving cellular function and offering a promising approach to advancing cardiac tissue engineering.

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