The spectrum of ischaemic cardiomyopathy, encompassing acute myocardial infarction to congestive heart failure is a significant clinical issue in the modern era. This group of diseases is an enormous source of morbidity and mortality and underlies significant healthcare costs worldwide. Cardiac regenerative therapy, whereby pro-regenerative cells, drugs or growth factors are administered to damaged and ischaemic myocardium has demonstrated significant potential, especially preclinically. While some of these strategies have demonstrated a measure of success in clinical trials, tangible clinical translation has been slow. To date, the majority of clinical studies and a significant number of preclinical studies have utilised relatively simple delivery methods for regenerative therapeutics, such as simple systemic administration or local injection in saline carrier vehicles. Here, we review cardiac regenerative strategies with a particular focus on advanced delivery concepts as a potential means to enhance treatment efficacy and tolerability and ultimately, clinical translation. These include (i) delivery of therapeutic agents in biomaterial carriers, (ii) nanoparticulate encapsulation, (iii) multimodal therapeutic strategies and (iv) localised, minimally invasive delivery via percutaneous transcatheter systems.

Bone marrow-derived mesenchymal stem cells (MSCs) have received much attention as a potential treatment for myocardial infarction because of their potential to integrate into the host myocardium and repair the injured heart. The mode of action of stem cell-mediated cardiac repair is still somewhat unclear, including the potential role of MSCs in neovascularization. The objective of this study was to determine the in vitro effect of MSCs on angiogenesis-related endothelial cell (EC) behavior, including migration, monolayer permeability, and vessel formation and stabilization. In a noncontact coculture system, we found that MSCs increase EC proliferation and migration, promoting early events of angiogenesis, while also decreasing EC monolayer permeability. Further, in a time- and dose-dependent manner, MSCs in direct coculture with ECs on Matrigel can increase the persistence of preexisting vessels by greater than threefold, with complex vessels remaining stable for more than 10 days. The results demonstrate that MSCs play an active role in the cellular processes involved in the formation, stabilization, and maturation of newly formed vessels. Further, these outcomes are not governed solely by either paracrine or direct contact effects and are both time and dose dependent.