The elucidation of factors that activate the regeneration of the adult mammalian heart is of major scientific and therapeutic importance. Here we found that epicardial cells contain a potent cardiogenic activity identified as follistatin-like 1 (Fstl1). Epicardial Fstl1 declines following myocardial infarction and is replaced by myocardial expression. Myocardial Fstl1 does not promote regeneration, either basally or upon transgenic overexpression. Application of the human Fstl1 protein (FSTL1) via an epicardial patch stimulates cell cycle entry and division of pre-existing cardiomyocytes, improving cardiac function and survival in mouse and swine models of myocardial infarction. The data suggest that the loss of epicardial FSTL1 is a maladaptive response to injury, and that its restoration would be an effective way to reverse myocardial death and remodelling following myocardial infarction in humans.

EBO with EWSs seems to be a reasonable and manageable treatment option for patients with prolonged pulmonary air leaks, including those with severe respiratory failure requiring mechanical ventilation.

Secondary lymphedema is a common disorder associated with acquired functional impairment of the lymphatic system. The goal of this study was to evaluate the therapeutic efficacy of aligned nanofibrillar collagen scaffolds (BioBridge) positioned across the area of lymphatic obstruction in guiding lymphatic regeneration. In a porcine model of acquired lymphedema, animals were treated with BioBridge scaffolds, alone or in conjunction with autologous lymph node transfer as a source of endogenous lymphatic growth factor. They were compared with a surgical control group and a second control group in which the implanted BioBridge was supplemented with exogenous vascular endothelial growth factor-C (VEGF-C). Three months after implantation, immunofluorescence staining of lymphatic vessels demonstrated a significant increase in lymphatic collectors within close proximity to the scaffolds. To quantify the functional impact of scaffold implantation, bioimpedance was used as an early indicator of extracellular fluid accumulation. In comparison to the levels prior to implantation, the bioimpedance ratio was significantly improved only in the experimental BioBridge recipients with or without lymph node transfer, suggesting restoration of functional lymphatic drainage. These results further correlated with quantifiable lymphatic collectors, as visualized by contrast-enhanced computed tomography. They demonstrate the therapeutic potential of BioBridge scaffolds in secondary lymphedema.

Background Delayed gadolinium (Gd) enhancement MRI (DEMRI) identifies non-viable myocardium, but is non-specific and may overestimate nonviable territory. Manganese (Mn2+)-enhanced MRI (MEMRI) denotes specific Mn2+ uptake into viable cardiomyocytes. We performed a dual-contrast myocardial assessment in a porcine ischemia-reperfusion (IR) model to test the hypothesis that combined DEMRI and MEMRI will identify viable infarct border zone (BZ) myocardium in vivo. Methods and Results Sixty-minute LAD ischemia-reperfusion injury (IR) was induced in 13 adult swine. Twenty-one days post-IR, 3T cardiac MRI was performed. MEMRI was obtained after injection (0.7 cc/kg) of Mn2+ contrast agent (EVP1001-1, Eagle Vision Pharmaceutical Corp.). DEMRI was then acquired after 0.2mmol/kg Gd injection. Left ventricular (LV) mass, infarct, and function were analyzed. Subtraction of MEMRI defect from DEMRI signal identified injured border zone myocardium. Explanted hearts were analyzed by 2,3,5-triphenyltetrazolium chloride (TTC) stain and tissue electron microscopy (TEM) to compare infarct, BZ, and remote myocardium. Average LV ejection fraction was reduced (30±7%). MEMRI and DEMRI infarct volumes correlated with TTC (MEMRI: r=0.78; DEMRI: r=0.75; p<0.004). MEMRI infarct volume percentage was significantly lower than DEMRI (14±4%* vs. 23±4%; *p<0.05). BZ MEMRI SNR was intermediate to remote and core infarct SNR (7.5±2.8* vs. 13.2±3.4 and 2.9±1.6; *p<0.0001), and DEMRI BZ SNR tended to be intermediate to remote and core infarct (8.4±5.4 vs. 3.3±0.6 and 14.3±6.6; p>0.05). TEM analysis exhibited preserved cell structure in BZ cardiomyocytes despite transmural DEMRI enhancement. Conclusions Dual-contrast MEMRI-DEMRI detects BZ viability within DEMRI infarct zones. This approach may identify injured, at-risk myocardium in ischemic cardiomyopathy.