Mobilization of stem and progenitor cells in cardiovascular diseases

Abstract

Circulating bone marrow (BM)-derived stem and progenitor cells (SPCs) participate in turnover of vascular endothelium and myocardial repair after acute coronary syndromes. Acute myocardial infarction (MI) produces a generalized inflammatory reaction, including mobilization of SPCs, increased local production of chemoattractants in the ischemic myocardium, as well as neural and humoral signals activating the SPC egress from the BM. Several types of circulating BM cells were identified in the peripheral blood, including hematopoietic stem cells, endothelial progenitor cells, mesenchymal stromal cells, circulating angiogenic cells and pluripotent very small embryonic-like cells; however, the contribution of circulating cells to the myocardial and endothelial repair is still unknown. The number and function of these cells is impaired in patients with diabetes and other cardiovascular risk factors, but can be improved by physical exercise and use of statins. The mobilization of SPCs in acute coronary syndromes and stable coronary artery disease seems to predict the clinical outcomes in selected groups of patients. Interpretation of the findings has to incorporate other factors that modulate the process of mobilization, such as coexisting diseases, age and medications. This review discusses the mobilization of SPCs in acute ischemia (MI, stroke), as well as in stable cardiovascular disease, and highlights the possibility of using the SPC as a marker of cardiovascular risk.

Exosomes and Cardiac Repair After Myocardial Infarction

“…The mobilization of BM-derived stem cells (BM-SCs) in patients with acute MI is considered a reparatory response, [21][22][23][24] and experimental studies have suggested an important role of BMSCs in cardiac repair response after MI. 13,20,[24][25][26][27][28][29] Nevertheless, the contribution of circulating cells to myocardial and endothelial repair is still incompletely understood. Moreover, the mobilization of endothelial progenitor cells correlates with the ischemic zone and not with the necrotic zone of patients after MI, 30 suggesting the possibility of an active mechanism originating from the ischemic border zone of the heart that is transmitted to the BM.…”

“…20,31 It is possible that ischemic tissue releases these chemoattractants, which create a gradient directing the cells to the site of injury. This mechanism was aptly demonstrated in vitro by positive migration of BM-SCs expressing early cardiac markers toward the homogenates of infarcted mouse myocardium enriched with stromal-derived factor-1, hepatocyte growth factor, and leukemia inhibitory factor.…”

“…This mechanism was aptly demonstrated in vitro by positive migration of BM-SCs expressing early cardiac markers toward the homogenates of infarcted mouse myocardium enriched with stromal-derived factor-1, hepatocyte growth factor, and leukemia inhibitory factor. 31 The complete mechanism of BM-SC mobilization is likely much more complicated because, first, the plasma levels of chemokines (stromal-derived factor-1) are not correlated with the extent of BM-SC mobilization 20 ; second, the measurement of plasma levels does not necessarily reflect local concentrations in the BM and ischemic tissue, which is more important for cell egress and homing; and third, as the recent evidence suggests, other signaling pathways and mechanisms, including exosomes and miRNAs, could promote trafficking and engraftment of BM and cardiac SCs, as we will discuss later.…”

Stem cell therapy for cardiovascular disease: the demise of alchemy and rise of pharmacology

“…The emerging question is whether inflammatory processes in the infarct zone promote or inhibit cell engraftment. On the one hand, inflammation acts as an activating factor for cell homing and proliferation via the production of chemoattractants (chemokines, cytokines, bioactive lipids; Cui and Madeddu, 2011;Ratajczak et al, 2012;Wojakowski et al, 2012) as well as complement activation (Ratajczak et al, 2012). On the other hand, a hostile microenvironment may impair cell engraftment, survival and differentiation (Swijnenburg et al, 2010;Sheikh et al, 2012).…”

Reactive Oxygen Species Adversely Impacts Bone Marrow Microenvironment in Diabetes

“…Investigation on the role of circulating angiogenic cells in CVD is complicated by the large heterogeneity of cells with direct and indirect pro-angiogenic capacities (117). Indeed, this pool includes CD34 + progenitor cells, Tie2 expressing monocytes, and mesenchymal stem cells (MSCs) from bone marrow (BM) and non-BM sources (26).…”