Composite scaffold provides a cell delivery platform for cardiovascular repair

TLDR

Control over cell engraftment, survival, and function remains critical for heart repair. The authors developed an adaptable platform that can be extended to deliver other reparative cells and used in quantitative studies of heart repair. They decellularized human myocardium preserving its extracellular matrix and mechanical properties, seeded the scaffold with fibrin‑hydrogel‑encapsulated mesenchymal progenitor cells, implanted the composite onto infarcted rat hearts, and conditioned the cells with low‑dose TGF‑β to promote an arteriogenic gene expression profile. The composite scaffold successfully delivered human MPCs, and preconditioned cells markedly increased vascular network formation and restored left ventricular systolic dimensions and contractility to baseline levels.

Abstract

Control over cell engraftment, survival, and function remains critical for heart repair. We have established a tissue engineering platform for the delivery of human mesenchymal progenitor cells (MPCs) by a fully biological composite scaffold. Specifically, we developed a method for complete decellularization of human myocardium that leaves intact most elements of the extracellular matrix, as well as the underlying mechanical properties. A cell–matrix composite was constructed by applying fibrin hydrogel with suspended cells onto decellularized sheets of human myocardium. We then implanted this composite onto the infarct bed in a nude rat model of cardiac infarction. We next characterized the myogenic and vasculogenic potential of immunoselected human MPCs and demonstrated that in vitro conditioning with a low concentration of TGF-β promoted an arteriogenic profile of gene expression. When implanted by composite scaffold, preconditioned MPCs greatly enhanced vascular network formation in the infarct bed by mechanisms involving the secretion of paracrine factors, such as SDF-1, and the migration of MPCs into ischemic myocardium, but not normal myocardium. Echocardiography demonstrated the recovery of baseline levels of left ventricular systolic dimensions and contractility when MPCs were delivered via composite scaffold. This adaptable platform could be readily extended to the delivery of other reparative cells of interest and used in quantitative studies of heart repair.