An off-the-shelf artificial cardiac patch improves cardiac repair after myocardial infarction in rats and pigs

Abstract

Cell therapy has been a promising strategy for cardiac repair after injury or infarction; however, low retention and engraftment of transplanted cells limit potential therapeutic efficacy. Seeding scaffold material with cells to create cardiac patches that are transplanted onto the surface of the heart can overcome these limitations. However, because patches need to be freshly prepared to maintain cell viability, long-term storage is not feasible and limits clinical applicability. Here, we developed an off-the-shelf therapeutic cardiac patch composed of a decellularized porcine myocardial extracellular matrix scaffold and synthetic cardiac stromal cells (synCSCs) generated by encapsulating secreted factors from isolated human cardiac stromal cells. This fully acellular artificial cardiac patch (artCP) maintained its potency after long-term cryopreservation. In a rat model of acute myocardial infarction, transplantation of the artCP supported cardiac recovery by reducing scarring, promoting angiomyogenesis, and boosting cardiac function. The safety and efficacy of the artCP were further confirmed in a porcine model of myocardial infarction. The artCP is a clinically feasible, easy-to-store, and cell-free alternative to myocardial repair using cell-based cardiac patches.

Agrin-Mediated Cardiac Regeneration: Some Open Questions

“…As an example, collagen scaffolds have been used to deliver vascular endothelial growth factor (VEGF) either by modifying the protein to include a collagen-binding domain or by seeding the scaffold with cells that have been genetically engineered to express VEGF, thereby extending the delivery time and promoting vascular growth in infarcted myocardial tissue [reviewed by Ye et al (2013)]. The last frontier would be that of employing the very latest technologies that created an acellular cardiac patch composed of synthetic microparticles containing secreted cardiac regenerative factors embedded in a scaffold formed by decellularized myocardial ECM (Huang et al, 2020), to allow release of agrin in the absence of the complications associated with cellular components. However, it remains to be determined whether any of the above patches would allow for the necessary time-restricted controlled delivery of recombinant agrin to the damaged heart, and local injection might still be the preferential and more efficient mean of administration, as recently shown in pig models of MI (Baehr et al, 2019).…”

3D printing of tissue engineering scaffolds: a focus on vascular regeneration

“…There are usually two methods for vascular tissue engineering: scaffold-based and scaffold-free approaches [ 6 ]. Compared to scaffold-free methods (e.g., decellularization methods [ 29 ]), scaffold-based strategy can direct cell colonization and proliferation through a pathway [ 12 ]. As we all know, 3D printing technology has made significant progress in the past decades.…”

Recent Development in Therapeutic Cardiac Patches

“…For cardiac stem therapy with patches, the difficulty in cell viability retaining becomes the limitation for clinical trials. To solve this problem, a strategy using synthetic cardiac stromal cells (synCSCs) was generated to fabricate an off-the-shelf therapeutic cardiac patch ( 40 ). Through the encapsulating of synCSCs on to the decellularized ECM, the potency of this fully acellular artificial cardiac patch (artCP) was well-maintained for a long time.…”