Highlights d Profiled spatiotemporal gene expression patterns in human cardiogenesis d Mapped cell-type distribution and spatial organization in the human embryonic heart d Thoroughly analyzed roles of diverse cell types in cardiac development d A publicly available web resource of the human embryonic heart

The alginate hydrogel is an effective and promising injectable delivery system in a myocardial infarction model. Sequential growth factor delivery of VEGF-A(165) and PDGF-BB induces mature vessels and improves cardiac function more than each factor singly. This may indicate clinical utility.

Rationale The ACCRUE (Meta-Analysis of Cell-based CaRdiac stUdiEs) is the first prospectively declared collaborative multinational database including individual data of patients (IPD) with ischemic heart disease treated with cell therapy. Objective We analyzed the safety and efficacy of intracoronary cell therapy after acute myocardial infarction (AMI) including IPDs from 12 randomized trials (ASTAMI, Aalst, BOOST, BONAMI, CADUCEUS, FINCELL, REGENT, REPAIR-AMI, SCAMI, SWISS-AMI, TIME, LATE-TIME; n=1252). Methods and Results The primary endpoint was freedom from combined major adverse cardiac and cerebrovascular events (MACCE; including all-cause death, re-AMI, stroke, and target vessel revascularization). The secondary endpoint was freedom from hard clinical endpoints (death, re-AMI, or stroke), assessed with random-effects meta-analyses and Cox regressions for interactions. Secondary efficacy endpoints included changes in end-diastolic volume (ΔEDV), end-systolic volume (ΔESV), and ejection fraction (ΔEF), analyzed with random-effects meta-analyses and analysis of covariance. We reported weighted mean differences between cell therapy and control groups. No effect of cell therapy on MACCE (14.0% vs. 16.3%, hazard ratio 0.86, 95%CI: 0.63;1.18) or death (1.4% vs 2.1%) or death/re-AMI/stroke (2.9% vs 4.7%) was identified in comparison to controls. No change in ΔEF (mean difference: 0.96%, 95%CI: −0.2;2.1), ΔEDV, or ΔESV was observed compared to controls. These results were not influenced by anterior AMI location, reduced baseline EF, or the use of MRI for assessing left ventricular parameters. Conclusions This meta-analysis of IPD from randomized trials in patients with recent AMI revealed that intracoronary cell therapy provided no benefit, in terms of clinical events or changes in left ventricular function.

To compare two situations with similar magnitudes of mitochondrial substrate flux but different blood oxygen contents, one-legged training was employed. Ten healthy subjects trained one leg under normobaric conditions and the other under hypobaric conditions. At each session the subjects trained each leg for 30 min. The absolute work intensity was the same for both legs and was chosen to correspond to 65% of the average (right and left) pretraining one-legged maximal work capacity. There were three to four training sessions per week for 4 wk. Muscle biopsies from each leg were taken before and after training and analyzed for fiber types, capillaries, myoglobin, and oxidative and glycolytic enzymes. The most striking finding was a greater increase of citrate synthase activity under hypobaric conditions than under normobaric conditions. In addition, the myoglobin content increased in the leg trained under hypobaric conditions, whereas it tended to decrease in the normobarically trained leg. Because both legs were trained at the same intensity, the oxygen turnover and the substrate flux through the carboxylic acid cycle and the respiratory chain must have been of similar magnitude. Thus a difference in substrate flux is less likely to have caused the differences in enzyme activities and myoglobin content between training under normobaric and hypobaric conditions. Instead, the stimulus seems to be related to the blood oxygen content or tension.

Adult human mesenchymal stem cells did not induce xenoreactivity in vitro in previously unexposed immunocompetent Sprague-Dawley rats. However, although mesenchymal stem cells are transplantable across allogeneic barriers, transplant rejection can occur in a xenogenic model. When transplanted into an immunoincompetent host, adult human mesenchymal stem cells showed persistent engraftment.

Skeletal muscle adaptations to high intensity knee extensor strength and/or endurance training in patients with chronic heart failure were investigated. Eleven patients with chronic heart failure were randomized into two groups and exercised the m. quadriceps femoris 3 days/week for 8 weeks. After training, the maximal exercise intensity tolerated on the ergometer cycle was raised from 99 (32) to 114 (40) watts (W, P < 0.05) for all 11 patients. Peak dynamic knee extensor work rate showed the greatest increase after endurance training (40%, P < 0.01). Maximal dynamic and isometric strength were elevated by 40-45% (P < 0.05) after strength training. The cross-sectional area of m. quadriceps femoris was increased in the strength-trained legs (9%, P < 0.05), and the capillary per fibre ratio of m. vastus lateralis was raised by 47 and 58% in the endurance-trained legs (P < 0.05). The oxidative enzyme activity in m. vastus lateralis was significantly raised above 50% after endurance training, whereas glycolytic enzyme activity was unaltered. The peripheral skeletal musculature in patients with chronic heart failure adapts fairly quickly to high intensity knee extensor training. This results in a marked rise in local, and a small rise in total work capacity, indicating maintained plasticity of skeletal muscle in chronic heart failure patients.

Recent studies have suggested that human embryonic stem cells (HESC) are immune-privileged and may thereby circumvent rejection. The expression of immunologically active molecules was studied by DNA microarray analysis and by flow cytometry. HESC were transplanted into immunologically competent mice and traced by fluorescence in-situ hybridization (FISH) and immunohistochemistry. The ability of HESC to directly and indirectly induce immune responses in CD4+ T-cells from naive and transplanted mice was studied. Their ability to induce immune responses of human CD4+ T-cells, when cultured in the presence of dendritic cells (DC) syngeneic to responder T-cells, was also analysed. HESC demonstrated expression of HLA class I and HLA class II genes, but the cell surface expression of HLA class II molecules was low even after incubation with IFNgamma. In wild-type mice, HESC could be demonstrated by FISH until 3 days after transplantation and were surrounded by heavy infiltrates of T-cells and macrophages. HESC induced a similar immune response as human fibroblast cells (HFib) on naive and immunized T-cells, both directly and in the presence of syngeneic DC. A similar response was observed in the allogeneic setting. It is concluded that HESC are immunologically inert and do not inhibit immune responses during direct or indirect antigen presentation, and they were acutely rejected in a xenogeneic setting.

Differences between the effects of training at sea level and at simulated altitude on performance and muscle structural and biochemical properties were investigated in 8 competitive cyclists who trained for 3-4 weeks, 4-5 sessions/week, each session consisting of cycling for 60-90 min continuously and 45-60 min intermittently. Four subjects, the altitude group (AG), trained in a hypobaric chamber (574 torr = 2300 m above sea level), and the other four at sea level (SLG). Before and after training work capacity was tested both at simulated altitude (574 torr) and at sea level, by an incremental cycle ergometer test until exhaustion. Work capacity was expressed as total amount of work performed. Venous blood samples were taken during the tests. Leg muscle biopsies were taken at rest before and after the training period. AG exhibited an increase of 33% in both sea level and altitude performance, while SLG increased 22% at sea level and 14% at altitude. Blood lactate concentration at a given submaximal load at altitude was significantly more reduced by training in AG than SLG. Muscle phosphofructokinase (PFK) activity decreased with training in AG but increased in SLG. All AG subjects showed increases in capillary density. In conclusion, work capacity at altitude was increased more by training at altitude than at sea level. Work capacity at sea level was at least as much improved by altitude as by sea level training. The improved work capacity by training at altitude was paralleled by decreased exercise blood lactate concentration, increased capillarization and decreased glycolytic capacity in leg muscle.