Stem cell-based therapies in ischemic heart diseases:N a focus on aspects of microcirculation and inflammation

Stem cells possessing the potential to replace damaged myocardium with functional myocytes have drawn increasing attention in the past decade in treating ischemic heart diseases; these diseases are the leading cause of morbidity and mortality in the world. The adult heart has recently been shown to contain a few cardiac stem cells (CSCs) that, in theory, suggest cardiac repair following acute myocardial infarction is possible if the CSC titer could be increased. Stem cell-based therapies, including hematopoietic stem cells and mesenchymal stem cells, were proven to be marginal and transitional. Multiple factors and mechanisms, rather than direct cardiac regeneration are involved in stem cell-mediated cardiac functional improvement. This review will focus on (1) the interaction between inflammation and stem cells; (2) the fate of stem cells at the microcirculatory level, and their subsequent influences on stem cell-based therapiesflow and oxygen supply. Early restoration of blood supply in the ischemic myocardium restricts the infarction size and improves clinical outcomes [13]. However, reperfusion itself is typically accompanied by acute inflammation and pulses of oxidative stress, resulting in further tissue damage, and referred to as reperfusion injury [5, 80]. Stem cells have increasingly attracted the attention of the bench scientist and the clinician interested in treating ischemic heart disease, due to their potential for repairing damaged cardiac tissue. However, the improvement of cardiac function has been proven to be marginal and transitional in both preclinical and clinical studies. The actual regeneration of damaged cardiac tissue was minimal, and below the level needed to achieve clinical benefits. This review will focus on the influence of inflammation, a major factor implicated in reperfusion injury, and microcirculation, the primary site where reperfusion injury is initially manifested, to further explore how these factors affect stem cell-based therapies.