Polyethylenimine-mediated gene delivery into human bone marrow mesenchymal stem cells from patients

Transplantation of mesenchymal stem cells (MSCs) derived from adult bone marrow has been proposed as a potential therapeutic approach for post-infarction left ventricular (LV) dysfunction. However, age-related functional decline of stem cells has restricted their clinical benefits after transplantation into the infarcted myocardium. The limitations imposed on patient cells could be addressed by genetic modification of stem cells. This study was designed to improve our understanding of genetic modification of human bone marrow derived mesenchymal stem cells (hMSCs) by polyethylenimine (PEI, branched with Mw 25 kD), one of non-viral vectors that show promise in stem cell genetic modification, in the context of cardiac regeneration for patients. We optimized the PEI-mediated reporter gene transfection into hMSCs, evaluated whether transfection efficiency is associated with gender or age of the cell donors, analysed the influence of cell cycle on transfection and investigated the transfer of therapeutic vascular endothelial growth factor gene (VEGF). hMSCs were isolated from patients with cardiovascular disease aged from 41 to 85 years. Optimization of gene delivery to hMSCs was carried out based on the particle size of the PEI/DNA complexes, N/P ratio of complexes, DNA dosage and cell viability. The highest efficiency with the cell viability near 60% was achieved at N/P ratio 2 and 6.0 μg DNA/cm 2. The average transfection efficiency for all tested samples, middle-age group (<65 years), old-age group (>65 years), female group and male group was 4.32%, 3.85%, 4.52%, 4.14% and 4.38%, respectively. The transfection efficiency did not show any correlation either with the age or the gender of the donors. Statistically, there were two subpopulations in the donors; and transfection efficiency in each subpopulation was linearly related to the cell percentage in S phase. No significant phenotypic differences were observed between these two subpopulations. Furthermore, PEI-mediated therapeutic gene VEGF transfer could significantly enhance the expression level.DFG/SFB/Transregio 37BMBF/0313191German Helmholtz AssociationDFG/0402710Ministry of Education/0312138 AMinistry of Economy (Mecklenburg-West Pommerania)/V220-630-08-TFMVF/S-035Marie Curie International Research Staff Exchange Scheme (IRSES, FP7-PEOPLE-2009-IRSES)Reference and Translation Center for Cardiac Stem Cell Therapy (RTC

Finanzmärkte, Unternehmungen, Informationen: Ergebnisse des Projektes im Wintersemester 2015/2016

Der vorliegende Beitrag der Wirtschaftswissenschaftlichen Schriften ist ein Sammelband, der die Beiträge der Studierenden des 2. Fachsemesters im Masterstudiengang General Management aus dem Wintersemester 2015/2016 umfasst. Die Einzelbeiträge wurden in einer zwei Monate dauernden Projektarbeit im Herbst 2015 erarbeitet und im Januar 2016 präsentiert. Der diesjährige Themenschwerpunkt lag auf dem Bereich "Banken", jedoch fanden auch andere Bereiche Eingang in das Spektrum der Arbeiten. Das Besondere dieser Ausarbeitungen liegt darin, dass sie in Form eines journalistischen Artikels aufgebaut sind und die Autoren die Aufgabe hatten, eine auch für Nichtfachleute geeignete Form der Darstellung zu finden. Besonderer Wert wurde auch auf einen gut lesbaren Schreibstil und die Vielfalt der Gestaltungsformen gelegt. Die Arbeiten liegen hier in der Originalversion vor und wurden nicht redigiert. Die Fakten wurden nach bestem Wissen ermittelt, jedoch besteht kein Anspruch auf Vollständigkeit

Indication for percutaneous aortic valve implantation

The incidence of valvular aortic stenosis has increased over the past decades due to improved life expectancy. Surgical aortic valve replacement is currently the only treatment option for severe symptomatic aortic stenosis that has been shown to improve survival. However, up to one third of patients who require lifesaving surgical aortic valve replacement are denied surgery due to high comorbidities resulting in a higher operative mortality rate. In the past such patients could only be treated with medical therapy or percutaneous aortic valvuloplasty, neither of which has been shown to improve mortality. With advances in interventional cardiology, transcatheter methods have been developed for aortic valve replacement with the goal of offering a therapeutic solution for patients who are unfit for surgical therapy. Currently there are two catheter-based treatment systems in clinical application (the Edwards SAPIEN aortic valve and the CoreValve ReValving System), utilizing either a balloon-expandable or a self-expanding stent platform, respectively

Abschlussbericht zum Verbundprojekt im Rahmen des Technologietransfer-Programms Leichtbau des Bundesministeriums für Wirtschaft und Energie

Im Rahmen des Verbundprojekts HyCoPE wurden neue Ansätze zur Reduzierung von Kosten und CO₂-Fußabdruck bei der Herstellung carbonfaserverstärkter Wasserstoff-Drucktanks entwickelt. Ziel war es, durch die ganzheitliche Betrachtung von Auslegungs- und Fertigungsprozessketten die Wettbewerbsfähigkeit der Brennstoffzellentechnologie zu erhöhen und so einen Beitrag zur emissionsfreien Mobilität zu leisten. Im Bereich Material wurde mit spuleninfiltrierten TowPregs eine kosteneffizientere und flexiblere Alternative zum Stand der Technik der konventionellen TowPreg-Materialien weiterentwickelt. Dazu wurde ein neuartiges Spulendesign und ein optimierter Infiltrationsprozess entwickelt, mit dem sich erstmals über 900 Meter Material in kurzer Zeit und hoher Qualität herstellen lassen. Parallel entstand ein angepasster Legekopf mit rollenbasierter Führung für die zuverlässige Verarbeitung des Materials. Im Bereich Simulation wurden neuartige Ansätze zur Erstellung von RVEs der Wickelstruktur betrachtet, um reale Material- und Struktureigenschaften in unterschiedliche Skalen von FE-Modellen zu mappen. Darüber hinaus wurde eine Methode zur Simulation von Kompaktierungseffekten entwickelt, die eine Analyse des veränderlichen Faservolumengehalts über die Dicke infolge der Fadenspannung und Lagenorientierung im Faserwickelprozess ermöglicht. Der Ansatz wurde durch Messungen an einem neuartigen Kompaktierungsprüfstand kalibriert und validiert. Zur Reduktion der Unsicherheiten im Fertigungsprozess wurde ein QS-Messsystem entwickelt, das die Erfassung des Faser-Ablagewinkels und weiterer strukturrelevanter Qualitätsmerkmale vor allem im Dombereich ermöglicht und durch eine Schnittstelle die realen Eigenschaften zurück in die Simulationsprozesskette übertragen kann. Das Messsystem wurde im Zuge der Herstellung der finalen Demonstratortanks in HyCoPE unter realistischen Einsatzbedingungen getestet

Acute Muscular Sarcocystosis: An International Investigation Among Ill Travelers Returning From Tioman Island, Malaysia, 2011-2012

A large outbreak of acute muscular sarcocystosis (AMS) among international tourists who visited Tioman Island, Malaysia, is described. Clinicians evaluating travelers returning ill from Malaysia with myalgia, with or without fever, should consider AMS in their differential diagnosi

Aging of human hematopoietic stem cells is linked to changes in Cdc42 activity

In this study, we characterize age-related phenotypes of human hematopoietic stem cells (HSC). We report increased frequencies of HSC, hematopoietic progenitor cells and lineage negative cells in the elderly but a decreased frequency of multi-lymphoid progenitors. Aged human HSC further exhibited a delay in initiating division ex vivo though without changes in their division kinetics. The activity of the small RhoGTPase Cdc42 was elevated in aged human hematopoietic cells and we identified a positive correlation between Cdc42 activity and the frequency of HSC upon aging. The frequency of human HSC polar for polarity proteins was, similar to the mouse, decreased upon aging, while inhibition of Cdc42 activity via the specific pharmacological inhibitor of Cdc42 activity, CASIN, resulted in re-polarization of aged human HSC with respect to Cdc42. Elevated activity of Cdc42 in aged HSC thus contributed to age-related changes in HSC. Xenotransplant, using NBSGW mice as recipients, showed elevated chimerism in recipients of aged compared to young HSC. Aged HSC treated with CASIN ex vivo displayed an engraftment profile similar to recipients of young HSC. Taken together, our work reveals strong evidence for a role of elevated Cdc42 activity in driving aging of human HSC, and similar to mice, this presents a likely possibility for attenuation of aging in human HSC

Sex-related Differences among Patients Undergoing Surgical Aortic Valve Replacement - A Propensity Score Matched Study.

OBJECTIVES We investigated the sex-related difference in characteristics and 2-year outcomes after surgical aortic valve replacement (SAVR) by propensity-score matching (PSM). METHODS Data from two prospective registries, INDURE and IMPACT, were merged, resulting in a total of 933 patients: 735 males and 253 females undergoing first-time SAVR. PSM was performed to assess the impact of sex on the SAVR outcomes, yielding 433 males and 243 females with comparable baseline characteristics. RESULTS Females had a lower body mass index (BMI; median 27.1 vs 28.0 kg/m2; p = 0.008), fewer bicuspid valves (52% vs 59%; p = 0.036), higher EuroSCORE II (mean 2.3 vs 1.8%; p < 0.001) and STS score (mean 1.6 vs 0.9%; p < 0.001), were more often in NYHA class III/IV (47% vs 30%; p < 0.001) and angina CCS III/IV (8.2% vs 4.4%; p < 0.001), but had a lower rate of myocardial infarction (1.9% vs 5.2%; p = 0.028) compared to males. These differences vanished after PSM, except for EuroSCORE II and STS scores, which were still significantly higher in females. Furthermore, females required smaller valves (median diameter 23.0 vs 25.0 mm, p < 0.001). There were no differences in the length of hospital stay (median 8 days) or ICU stay (median 24 vs 25 hours) between both sexes. At two years, post-SAVR outcomes were comparable between males and females, even after PSM. CONCLUSIONS Despite females presenting with a significantly higher surgical risk profile, 2-year outcomes following SAVR were comparable between males and females

Multimodal monitoring of neutrophil activity during cardiac surgery

Cardiac surgery and the associated ischemia-reperfusion injury trigger an inflammatory response, which, in turn, can contribute to organ damage, prolonged hospitalization, and mortality. Therefore, the present study performed comprehensive monitoring of neutrophil-related inflammation in patients who underwent aortic valve surgery, including extracorporeal circulation. Neutrophil-related inflammation, as well as alterations in cellular physiology, phenotype, and function, were analyzed by flow cytometry, ELISA, and microscopy. Neutrophil activation occurred intraoperatively and preceded the upregulation of conventional inflammatory markers such as C-reactive protein and interleukin-6. Perioperatively, neutrophils maintained a stable response to platelet-activating factor (PAF) with regard to CD11b and CD66b expression but showed a decreased response in CD10. Postoperatively, neutrophils exhibited marked alterations in PAF-induced depolarization, while reactive oxygen species generation and phagocytic activity remained largely stable. Surprisingly, platelet-neutrophil complex formation was severely impaired intraoperatively but returned to normal levels postoperatively. Further studies are needed to elucidate the implications of these intraoperative and postoperative changes in neutrophil and platelet activity with respect to a potential immune dysfunction that temporarily increases susceptibility to infectious or hemostatic complications

Intraoperative haemoadsorption for antithrombotic drug removal during cardiac surgery: initial report of the international safe and timely antithrombotic removal (STAR) registry

Intraoperative antithrombotic drug removal by haemoadsorption is a novel strategy to reduce perioperative bleeding in patients on antithrombotic drugs undergoing cardiac surgery. The international STAR registry reports real-world clinical outcomes associated with this application. All patients underwent cardiac surgery before completing the recommended washout period. The haemoadsorption device was incorporated into the cardiopulmonary bypass (CPB) circuit. Patients on P2Y12 inhibitors comprised group 1, and patients on direct-acting oral anticoagulants (DOAC) group 2. Outcome measurements included bleeding events according to standardised definitions and 24-hour chest-tube-drainage (CTD). 165 patients were included from 8 institutions in Austria, Germany, Sweden, and the UK. Group 1 included 114 patients (62.9 ± 11.6years, 81% male) operated at a mean time of 33.2 h from the last P2Y12 inhibitor dose with a mean CPB duration of 117.1 ± 62.0 min. Group 2 included 51 patients (68.4 ± 9.4years, 53% male), operated at a mean time of 44.6 h after the last DOAC dose, with a CPB duration of 128.6 ± 48.4 min. In Group 1, 15 patients experienced a BARC-4 bleeding event (13%), including 3 reoperations (2.6%). The mean 24-hour CTD was 651 ± 407mL. In Group 2, 8 patients experienced a BARC-4 bleeding event (16%) including 4 reoperations (7.8%). The mean CTD was 675 ± 363mL. This initial report of the ongoing STAR registry shows that the intraoperative use of a haemoadsorption device is simple and safe, and may potentially mitigate the expected high bleeding risk of patients on antithrombotic drugs undergoing cardiac surgery before completion of the recommended washout period.Clinical registration number: ClinicalTrials.gov identifier: NCT05077124.Graphical AbstractOpen Access funding enabled and organized by Projekt DEAL.Universitätsklinik München (6933