Intramyocardial injection of pre-cultured endothelial progenitor cells and mesenchymal stem cells inside alginate/gelatin microspheres induced angiogenesis in infarcted rabbits

OpenAlex İngilizce

BACKGROUND: Using several strategies, the stimulation of angiogenesis can alleviate the pathological complications of post-myocardial ischemia. Here, endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) were pre-cultured inside the alginate/gelatin (Alg/Gel) microspheres in the presence of SDF-1α for 7 days, and their angiogenesis potential was monitored in infarcted rabbits. METHODS: The decapsulated cells were monitored in terms of cell dynamic growth and angiogenesis potential in vitro and after injection into ischemic myocardium in rabbits. RESULTS: Based on the data, 7-day incubation inside the Alg/Gel microspheres led to the stimulation of angiogenesis profile (Ang-1↑, -2↑, Tie-2↑), migration (MMP-2↑, and − 9↑), and autophagic response (Beclin-1↑, LC3↑, and p-62↓) in EPCs containing groups in the presence of SDF-1α. PCR array analysis revealed the expression of angiogenesis-related genes in the presence of SDF-1α. These features coincided with the stimulation of in vitro tubulogenesis properties in EPCs and EPCs + SDF-1α groups. The injection of cells from different groups into the infarcted rabbits led to the reduction of fibrotic area in ischemic myocardium in MSCs-bearing groups, and these effects were intensified in the presence of SDF-1α. Pre-treatment of EPCs and MSCs increased the recruited immune cells into the ischemic area within the myocardium. It was suggested that SDF-1α stimulated the local vascular density (CD31 capillaries, and α-SMA arterioles) in EPCs-bearing groups compared to MSCs and MSCs + SDF-1α groups. CONCLUSIONS: These data indicate that pre-culture of EPCs and MSCs inside the Alg-based hydrogels can increase the regenerative potential of these cells, especially when exposed to stimulatory cytokines such as SDF-1α for the alleviation of ischemic changes.