The primary cause of death among chronic diseases worldwide is ischemic cardiovascular diseases, such as stroke and myocardial infarction. Recent evidence indicates that adult stem cell therapies involving cardiovascular regeneration represent promising strategies to treat cardiovascular diseases. Owing to their immunomodulatory properties and vascular repair capabilities, mesenchymal stem cells (MSCs) are strong candidate therapeutic stem cells for use in cardiovascular regeneration. However, major limitations must be overcome, including their very low survival rate in ischemic lesion. Various attempts have been made to improve the poor survival and longevity of engrafted MSCs. In order to develop novel therapeutic strategies, it is necessary to first identify stem cell modulators for intracellular signal triggering or niche activation. One promising therapeutic strategy is the priming of therapeutic MSCs with stem cell modulators before transplantation. Another is a tissue engineering-based therapeutic strategy involving a cell scaffold, a cell-protein-scaffold architecture made of biomaterials such as ECM or hydrogel, and cell patch- and 3D printing-based tissue engineering. This review focuses on the current clinical applications of MSCs for treating cardiovascular diseases and highlights several therapeutic strategies for promoting the therapeutic efficacy of MSCs in vitro or in vivo from cell priming to tissue engineering strategies, for use in cardiovascular regeneration.

Accumulating evidence indicates that acute and chronic uncontrolled overproduction of oxidative stress-related factors including reactive oxygen species (ROS) causes cardiovascular diseases (CVDs), atherosclerosis, and diabetes. Moreover ROS mediate various signaling pathways underlying vascular inflammation in ischemic tissues. With respect to stem cell-based therapy, several studies clearly indicate that modulating antioxidant production at cellular levels enhances stem/progenitor cell functionalities, including proliferation, long-term survival in ischemic tissues, and complete differentiation of transplanted cells into mature vascular cells. Recently emerging therapeutic strategies involving adult stem cells, including endothelial progenitor cells (EPCs), for treating ischemic CVDs have highlighted the need to control intracellular ROS production, because it critically affects the replicative senescence of ex vivo expanded therapeutic cells. Better understanding of the complexity of cellular ROS in stem cell biology might improve cell survival in ischemic tissues and enhance the regenerative potentials of transplanted stem/progenitor cells. In this review, we will discuss the nature and sources of ROS, drug-based therapeutic strategies for scavenging ROS, and EPC based therapeutic strategies for treating oxidative stress-related CVDs. Furthermore, we will discuss whether primed EPCs pretreated with natural ROS-scavenging compounds are crucial and promising therapeutic strategies for vascular repair.

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Cardiovascular diseases (CVDs), including atherosclerosis, stroke, and myocardial infarction, is a major cause of death worldwide. In aspects of cell therapy against CVD, it is generally accepted that endothelial progenitor cells (EPCs) are potent neovascular modulators in ischemic tissues. In response to ischemic injury signals, EPCs located in a bone marrow niche migrate to injury sites and form new vessels by secreting various vasculogenic factors including VEGF, SDF-1, and FGF, as well as by directly differentiating into endothelial cells. Nonetheless, in ischemic tissues, most of engrafted EPCs do not survive under harsh ischemic conditions and nutrient depletion. Therefore, an understanding of diverse EPC-related cytoprotective mediators underlying EPC homeostasis in ischemic tissues may help to overcome current obstacles for EPC-mediated cell therapy for CVDs. Additionally, to enhance EPC's functional capacity at ischemic sites, multiple strategies for cell survival should be considered, that is, preconditioning of EPCs with function-targeting drugs including natural compounds and hormones, virus mediated genetic modification, combined therapy with other stem/progenitor cells, and conglomeration with biomaterials. In this review, we discuss multiple cytoprotective mediators of EPC-based cardiovascular repair and propose promising therapeutic strategies for the treatment of CVDs.