Perfusion defect size predicts engraftment but not early retention of intra-myocardially injected cardiosphere-derived cells after acute myocardial infarction

Therapeutic cell retention and engraftment are critical for myocardial regeneration. Underlying mechanisms, including the role of tissue perfusion, are not well understood. In Wistar Kyoto rats, syngeneic cardiosphere-derived cells (CDCs) were injected intramyocardially, after experimental myocardial infarction. CDCs were labeled with [18F]-FDG (n = 7), for quantification of 1-h retention, or with sodium-iodide-symporter gene (NIS; n = 8), for detection of 24-h engraftment by reporter imaging. Perfusion was imaged simultaneously. Infarct size was 37 ± 9 and 38 ± 9% of LV in FDG and NIS groups. Cell signal was located in the infarct border zone in all animals. No significant relationship was observed between infarct size and 1-h CDC retention (r = −0.65; P = 0.11). However, infarct size correlated significantly with 24-h engraftment (r = 0.75; P = 0.03). Residual perfusion at the injection site was not related to cell retention/engraftment. Larger infarcts are associated with improved CDC engraftment. This observation encourages further investigation of microenvironmental conditions after ischemic damage and their role in therapeutic cell survival

Secretome of apoptotic peripheral blood cells (APOSEC) confers cytoprotection to cardiomyocytes and inhibits tissue remodelling after acute myocardial infarction: a preclinical study

Heart failure following acute myocardial infarction (AMI) is a major cause of morbidity and mortality. Our previous observation that injection of apoptotic peripheral blood mononuclear cell (PBMC) suspensions was able to restore long-term cardiac function in a rat AMI model prompted us to study the effect of soluble factors derived from apoptotic PBMC on ventricular remodelling after AMI. Cell culture supernatants derived from irradiated apoptotic peripheral blood mononuclear cells (APOSEC) were collected and injected as a single dose intravenously after myocardial infarction in an experimental AMI rat model and in a porcine closed chest reperfused AMI model. Magnetic resonance imaging (MRI) and echocardiography were used to quantitate cardiac function. Analysis of soluble factors present in APOSEC was performed by enzyme-linked immunosorbent assay (ELISA) and activation of signalling cascades in human cardiomyocytes by APOSEC in vitro was studied by immunoblot analysis. Intravenous administration of a single dose of APOSEC resulted in a reduction of scar tissue formation in both AMI models. In the porcine reperfused AMI model, APOSEC led to higher values of ejection fraction (57.0 vs. 40.5%, p < 0.01), a better cardiac output (4.0 vs. 2.4 l/min, p < 0.001) and a reduced extent of infarction size (12.6 vs. 6.9%, p < 0.02) as determined by MRI. Exposure of primary human cardiac myocytes with APOSEC in vitro triggered the activation of pro-survival signalling-cascades (AKT, Erk1/2, CREB, c-Jun), increased anti-apoptotic gene products (Bcl-2, BAG1) and protected them from starvation-induced cell death. Intravenous infusion of culture supernatant of apoptotic PBMC attenuates myocardial remodelling in experimental AMI models. This effect is probably due to the activation of pro-survival signalling cascades in the affected cardiomyocytes

Programmed cell death and its role in inflammation

Cell death plays an important role in the regulation of inflammation and may be the result of inflammation. The maintenance of tissue homeostasis necessitates both the recognition and removal of invading microbial pathogens as well as the clearance of dying cells. In the past few decades, emerging knowledge on cell death and inflammation has enriched our molecular understanding of the signaling pathways that mediate various programs of cell death and multiple types of inflammatory responses. This review provides an overview of the major types of cell death related to inflammation. Modification of cell death pathways is likely to be a logical therapeutic target for inflammatory diseases

Modelling of future mass balance changes of Norwegian glaciers by application of a dynamical–statistical model

The long-term behaviour of Norwegian glaciers is reflected by the long mass-balance records provided by the Norwegian Water Resources and Energy Directorate. These show positive annual mass balances in the 1980s and 1990s at maritime glaciers followed by rapid mass loss since 2000. This study assesses the influence of various atmospheric variables on mass changes of selected Norwegian glaciers by correlation- and cross-validated stepwise multiple regression analyses. The atmospheric variables are constructed from reanalyses by the National Centers for Environmental Prediction and the European Centre for Medium-Range Weather Forecasts. Transfer functions determined by the multiple regression are applied to predictors derived from a multi-model ensemble of climate projections to estimate future mass-balance changes until 2100. The statistical relationship to the North Atlantic Oscillation (NAO), the strongest predictor, is highest for maritime glaciers and less for more continental ones. The mass surplus in the 1980s and 1990s can be attributed to a strong NAO phase and lower air temperatures during the ablation season. The mass loss since 2000 can be explained by an increase of summer air temperatures and a slight weakening of the NAO. From 2000 to 2100 the statistical model predicts predicts changes for glaciers in more continental settings of c. −20 m w.e. (water equivalent) or 0.2 m w.e./a. The corresponding range for their more maritime counterparts is −0.5 to +0.2 m w.e./a. Results from Bayesian classification of observed atmospheric states associated with high melt or high accumulation in the past into different simulated climates in the future suggest that climatic conditions towards the end of the twenty-first century favour less winterly accumulation and more ablation in summer. The posterior probabilities for high accumulation at the end of the twenty-first century are typically 1.5–3 times lower than in the twentieth century while the posterior probabilities for high melt are often 1.5–3 times higher at the end of the twenty-first century than in the twentieth and early twenty-first century