Bone marrow-derived cells which may be involved in cardiac repair/regeneration after ischaemic injury must undergo mobilisation into peripheral blood with subsequent homing and engraftment into the target organ. Mobilisation of the heterogeneous population of stem/progenitor cells in endothelial injury or myocardial ischaemia has been described recently. The number of circulating stem/progenitor cells reflects the endothelial damage, and turnover may be a surrogate marker reflecting the burden of cardiovascular risk factors and prognostic markers in stable coronary heart disease and acute coronary syndromes. Acute coronary syndromes are associated with increased levels of inflammatory and haematopoietic cytokines which, in turn, can mobilise progenitor cells from the bone marrow. Myocardial infarction increases the number of endothelial progenitor cells and other less well-defined subpopulations, such as CD34/c-kit⁺ and CD34/CXCR4⁺ cells, which may take part in cardiac repair after ischaemic injury. Data on mobilisation of stem/progenitor cells in acute coronary syndromes are summarised here. Cell types, mechanisms of mobilisation, homing and engraftment are discussed and their relevance to clinical outcomes.

Background: Diagnosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) requires both clinical evidence of acute myocardial infarction (AMI) and demonstration of non-obstructive coronary arteries using angiography. We compared the clinical features, treatments, and three-year outcomes in patients with MINOCA and myocardial infarction with obstructive coronary artery disease (MI-CAD). Methods: We retrospectively analyzed data for 205,606 hospitalized patients with AMI. MINOCA was indicated as a working diagnosis in 6063 patients (2.94% of all AMI patients). For the control group we included 160,886 patients with MI-CAD. We evaluated the baseline characteristics, medication management options, outcomes, and readmission causes at 36 months follow-up. Results: Patients in the MINOCA group were younger. Females constituted a greater proportion of patients in the MINOCA group when compared to MI-CAD patients. STEMI during admission was diagnosed less frequently in the MINOCA group when compared to the MI-CAD group. All-cause mortality at 12 months was higher in the MINOCA group (10.94% vs. 9.54%, p < 0.001). At 36 months, there was no difference in the all-cause mortality rates (MINOCA 16.18% vs. MI-CAD 14.93%, p = 0.081). All-cause readmission rates were lower in the MINOCA group when compared to the MI-CAD group at both 12 months (45.19% vs. 54.33%, p < 0.001) and 36 months follow-up (56.42% vs. 66.66%, p < 0.001). Conclusions: This is the first description of the clinical features, treatments, and three-year outcomes in a large population of Polish patients. The main finding of this study was a relatively low rate of MINOCA, with high rates of adverse events both at 12 and 36 months follow-up.

There is a lack of studies directly comparing the effect of air pollution on acute coronary syndrome (ACS) occurrence in industrial and non-industrial areas. A comparison of association of air pollution exposure with ACS in two cohorts of industrially different areas. The study covered 6,000,000 person-years of follow-up and five pollutants between 2008 and 2017. A time series regression analysis with 7-lag was used to assess the effects air pollution on ACS. A total of 9046 patients with ACS were included in the analysis, of whom 3895 (43.06%) had ST-elevation myocardial infarction (STEMI) - 45.39% from non-industrial area, and 42.37% from industrial area; and 5151 (56.94%) had non-ST-elevation myocardial infarction (NSTEMI) - 54.61% from non-industrial area and 57.63% from industrial area. The daily concentrations of PM_2.5, PM₁₀, NO₂, SO₂, CO were higher in industrial than in non-industrial area (P < 0.001). In non-industrial area, an increase of 10 μg/m³ of NO₂ concentration (Odds Ratio (OR) = 1.126, 95%CI = 1.009-1.257; P = 0.034, lag-0) and an increase of 1 mg/m³ in CO concentration (RR = 1.055, 95%CI = 1.010-1.103; P = 0.017, lag-0) were associated with an increase in the number of hospitalization due to NSTEMI (for industrial area increase of 10 μg/m³ in NO₂ (OR = 1.062, 95%CI = 1.020-1.094; P = 0.005, lag-0), SO₂ (OR = 1.061, 95%CI = 1.010-1.116; P = 0.018, lag-4), PM₁₀ (OR = 1.010, 95%CI = 1.001-1.030; P = 0.047, lag-6). In STEMI patients in industrial area, an increased hospitalization was found to be associated with an increase of 10 μg/m³ in SO₂ (OR = 1.094, 95%CI = 1.030-1.162; P = 0.002, lag-1), PM_2.5 (OR = 1.041, 95%CI = 1.020-1.073; P < 0.001, lag-1), PM₁₀ (OR = 1.030, 95%CI = 1.010-1.051; P < 0.001, lag-1). No effects of air pollution on the number of hospitalization due to STEMI were noted from non-industrial area. The risk of air pollution-related ACS was higher in industrial over non-industrial area. The effect of NO₂ on the incidence of NSTEMI was observed in both areas. In industrial area, the effect of PMs and SO₂ on NSTEMI and STEMI were also observed. A clinical effect was more delayed in time in patients with NSTEMI, especially after exposure to PM₁₀. Chronic exposure to air pollution may underlie the differences in the short-term effect between particulate air pollution impact on the incidence of STEMI.

VSELs are a population of rare Oct-4+CXCR4+ CD133+lin-CD45- cells that are deposited during early embryogenesis in developing organs/tissues as a reserve population of pluripotent stem cells for regeneration. We reported recently that they are mobilized into peripheral blood during acute myocardial infarction (AMI) in mice and humans. However, although freshly isolated VSELs in experimental AMI mouse models improve cardiac function, the number of these cells is limited and an ex vivo expansion strategy is needed to employ these cells more efficiently for cardiac regeneration. The aim of this study was to establish an efficient method to expand ex vivo BM-derived very small embryonic-like stem cells (VSELs) into cardiomyocytes. VSELs, highly purified by FACS from the bone marrow of GFP transgenic mice, were expanded over C2C12 cell line myoblasts and exposed to cardiac differentiating media. The changes in gene expression during cardiac differentiation of VSELs were evaluated by RTQ-PCR, immunostaining and gene array analysis. We developed an efficient, two-step, ex vivo expansion/differentiation model of BM-derived VSELs into cardiomyocytes. First, purified GFP+ VSELs are plated over C2C12 murine cell line myoblasts, where they expand and differentiate into characteristic spheres. Subsequently, cells from these spheres are expanded on cardiac differentiating media into cardiomyocytes. This study demonstrates that murine BM-derived VSELs can be efficiently expanded in vitro and differentiated into cardiomyocytes.

Very small embryonic-like cells (VSELs) are a population of stem cells residing in the bone marrow (BM) and several organs, which undergo mobilization into peripheral blood (PB) following acute myocardial infarction and stroke. These cells express markers of pluripotent stem cells (PSCs), such as Oct-4, Nanog, and SSEA-1, as well as early cardiac, endothelial, and neural tissue developmental markers. VSELs can be effectively isolated from the BM, umbilical cord blood, and PB. Peripheral blood and BM-derived VSELs can be expanded in co-culture with C2C12 myoblast feeder layer and undergo differentiation into cells from all three germ layers, including cardiomyocytes and vascular endothelial cells. Isolation of VSLEs using fluorescence-activated cell sorting multiparameter live cell sorting system is dependent on gating strategy based on their small size and expression of PSC and absence of hematopoietic lineage markers. VSELs express early cardiac and endothelial lineages markers (GATA-4, Nkx2.5/Csx, VE-cadherin, and von Willebrand factor), SDF-1 chemokine receptor CXCR4, and undergo rapid mobilization in acute MI and ischemic stroke. Experiments in mice showed differentiation of BM-derived VSELs into cardiac myocytes and effectiveness of expanded and pre-differentiated VSLEs in improvement of left ventricular ejection fraction after myocardial infarction.