Enhanced engraftment and repairing ability of human adipose-derived stem cells, conveyed by pharmacologically active microcarriers continuously releasing HGF and IGF-1, in healing myocardial infarction in rats

One of the main cause of ineffective cell therapy in repairing the damaged heart is the poor yield of grafted cells. To overcome this drawback, rats with 4-week-old myocardial infarction (MI) were injected in the border zone with human adipose-derived stem cells (ADSCs) conveyed by poly(lactic-co-glycolic acid) microcarriers (PAMs) releasing hepatocyte growth factor (HGF) and insulin-like growth factor-1 (IGF-1) (GFsPAMs). According to treatments, animals were subdivided into different groups: MI-ADSC, MI-ADSC/PAM, MI-GFsPAM, MI-ADSC/GFsPAM, and untreated MI-V. Two weeks after injection, a 31% increase in ADSC engraftment was observed in MI-ADSC/PAM compared with MI-ADSC (p < 0.05). A further ADSC retention was obtained in MI-ADSC/GFsPAM with respect to MI-ADSC (106%, p < 0.05) and MI-ADSC/PAM (57%, p < 0.05). A 130% higher density of blood vessels of medium size was present in MI-ADSC/GFsPAM compared with MI-ADSC (p < 0.01). MI-ADSC/GFsPAM also improved, albeit slightly, left ventricular remodeling and hemodynamics with respect to the other groups. Notably, ADSCs and/or PAMs, with or without HGF/IGF-1, trended to induce arrhythmias in electrically driven, Langendorff-perfused, hearts of all groups. Thus, PAMs releasing HGF/IGF-1 markedly increase ADSC engraftment 2 weeks after injection and stimulate healing in chronically infarcted myocardium, but attention should be paid to potentially negative electrophysiological consequences.