Human mesenchymal stromal cells and derived extracellular vesicles: Translational strategies to increase their proangiogenic potential for the treatment of cardiovascular disease

Abstract

Abstract Mesenchymal stromal cells (MSCs) offer great potential for the treatment of cardiovascular diseases (CVDs) such as myocardial infarction and heart failure. Studies have revealed that the efficacy of MSCs is mainly attributed to their capacity to secrete numerous trophic factors that promote angiogenesis, inhibit apoptosis, and modulate the immune response. There is growing evidence that MSC-derived extracellular vesicles (EVs) containing a cargo of lipids, proteins, metabolites, and RNAs play a key role in this paracrine mechanism. In particular, encapsulated microRNAs have been identified as important positive regulators of angiogenesis in pathological settings of insufficient blood supply to the heart, thus opening a new path for the treatment of CVD. In the present review, we discuss the current knowledge related to the proangiogenic potential of MSCs and MSC-derived EVs as well as methods to enhance their biological activities for improved cardiac tissue repair. Increasing our understanding of mechanisms supporting angiogenesis will help optimize future approaches to CVD intervention. Significance statement Mesenchymal stromal cells (MSCs) are currently being evaluated in clinical trials for the treatment of numerous diseases. Their therapeutic potential is mainly due to the factors they secrete. Studies have demonstrated that MSCs also produce extracellular vesicles that carry proteins, metabolites, lipids, and various RNAs. Based on their multifunctional properties, extracelullar vesicles are of great importance and interest in the development of future medicine. This study provides an overview of the current knowledge on the therapeutic potential of MSCs and MSC-derived extracelullar vesicles, as well as methods for improving their biological activities to promote angiogenesis and tissue repair.