Rapid manufacturing of angiogenic cellular collagen patches for ischemic cardiomyopathy.

BACKGROUND

One in ten Americans carry a lifetime risk of ischemic heart failure, the most severe form of ischemic heart disease. Carrying a nearly 50% five‑year mortality rate, no interventional therapy exists to treat the underlying cause, microvascular malperfusion. In efforts to combat microvascular malperfusion, our group has utilized synergistic application of endothelial progenitor cells (EPCs) and smooth muscle cells (SMCs) to induce angiogenesis in ischemic myocardium.

METHODS

Cells are then embedded into a rapidly manufacturable compressed collagen (CC) patch to provide a biosimilar scaffold ready for transplantation. The performance of the cellular compressed collagen patch was then tested on a rodent acute myocardial infarction model of ischemic heart failure.

RESULTS

By post‑transplantation Day 28, the cellular CC patch improved left ventricular ejection fraction when compared to an acellular CC patch and control (cellular: 49.1 ± 1.8%; acellular: 38.0 ± 2.6%; control: 39.2 ± 2.1%; ANOVA P = .0006). Cellular CC patch transplantation also induced mature angiogenesis as shown by arteriolar density (cellular: 1084 ± 98 αSMA+vWF+/mm2; acellular: 338 ± 57 αSMA+vWF+/mm2; control: 449 ± 39 αSMA+vWF+/mm2; ANOVA P = .0003) and vascular maturation index (cellular: 0.67 ± 0.04; acellular: 0.48 ± 0.02; and control: 0.46 ± 0.04, P = .001).

CONCLUSIONS

In conclusion, transplantation of a rapidly manufacturable EPC‑SMC‑based compressed collagen patch effectively rescues myocardial function by enhancing neovascularization and attenuating post‑infarction myocardial injury.