Noninvasive in vivo tracking of mesenchymal stem cells and evaluation of cell therapeutic effects in a murine model using a clinical 3.0 T MRI

Cardiac cell therapy with mesenchymal stem cells (MSCs) represents a promising treatment approach for endstage heart failure. However, little is known about the underlying mechanisms and the fate of the transplanted cells. The objective of the presented work is to determine the feasibility of magnetic resonance imaging (MRI) and in vivo monitoring after transplantation into infarcted mouse hearts using a clinical 3.0 T MRI device. The labeling procedure of bone marrow-derived MSCs with micron-sized paramagnetic iron oxide particles (MPIOs) did not affect the viability of the cells and their cell type-defining properties when compared to unlabeled cells. Using a clinical 3.0 T MRI scanner equipped with a dedicated small animal solenoid coil, 105 labeled MSCs could be detected and localized in the mouse hearts for up to 4 weeks after intramyocardial transplantation. Weekly ECG-gated scans using T1-weighted sequences were performed, and left ventricular function was assessed. Histological analysis of hearts confirmed the survival of labeled MSCs in the target area up to 4 weeks after transplantation. In conclusion, in vivo tracking of labeled MSCs using a clinical 3.0 T MRI scanner is feasible. In combination with assessment of heart function, this technology allows the monitoring of the therapeutic efficacy of regenerative therapies in a small animal model. </jats:p

Dynamic Support Culture of Murine Skeletal Muscle-derived Stem Cells Improves Their Cardiogenic Potential In Vitro

Ischemic heart disease is the main cause of death in western countries and its burden is increasing worldwide. It typically involves irreversible degeneration and loss of myocardial tissue leading to poor prognosis and fatal outcome. Autologous cells with the potential to regenerate damaged heart tissue would be an ideal source for cell therapeutic approaches. Here, we compared different methods of conditional culture for increasing the yield and cardiogenic potential of murine skeletal muscle-derived stem cells. A subpopulation of nonadherent cells was isolated from skeletal muscle by preplating and applying cell culture conditions differing in support of cluster formation. In contrast to static culture conditions, dynamic culture with or without previous hanging drop preculture led to significantly increased cluster diameters and the expression of cardiac specific markers on the protein and mRNA level. Whole-cell patch-clamp studies revealed similarities to pacemaker action potentials and responsiveness to cardiac specific pharmacological stimuli. This data indicates that skeletal muscle-derived stem cells are capable of adopting enhanced cardiac muscle cell-like properties by applying specific culture conditions. Choosing this route for the establishment of a sustainable, autologous source of cells for cardiac therapies holds the potential of being clinically more acceptable than transgenic manipulation of cells

Canım

Selami İzzet'in Akşam'da tefrika edilen Canım adlı romanıTelif hakları nedeniyle romanın tam metni verilememiştir

Abstracts from the 8th International Conference on cGMP Generators, Effectors and Therapeutic Implications

This work was supported by a restricted research grant of Bayer AG

Auslastungsorientierte Erntelogistik: Routenplanung und Disposition von Feldhäckslern, Überladewagen und Transportfahrzeugen mit Synchronisationsnebenbedingungen

Agricultural contractors are logistics service providers for various field operations in agriculture. Restrictions imposed by nature, lack of personnel, high-priced agricultural machinery and small margins require contractors to make efficient use of their fleet of agricultural machinery. In order to achieve a short completion time, as is particularly necessary for harvesting, the dispatcher aims to minimize travel times between the operating locations and to increase the utilization of harvesting machines, e.g. forage harvesters and combine harvesters. This paper examines the harvesting process involving forage harvesters and support vehicles (transfer vehicles and transport vehicles). Here, if insufficient support vehicles are available, the forage harvester needs to pause operation on the field while waiting for a support vehicle that can receive the harvested biomass. Typically, teams of harvesters and support vehicles are assembled prior to the start of the harvesting process and remain in this constellation until all fields in the planning period have been harvested. In this study, we investigate the time savings when vehicles are not tied to their team and can thereby harvest each field in a new constellation of vehicles. This paper presents two mathematical models describing the harvesting process with forage harvesters, transfer vehicles and transporters with a focus on the utilization of the forage harvesters with fixed and variable team compositions, respectively. These models are solved via mixed-integer programming with the Gurobi solver.Landwirtschaftliche Lohnunternehmer sind Logistikdienstleister für verschiedene Feldarbeiten in der Landwirtschaft. Naturgegebene Restriktionen, Personalmangel, hochpreisige Landmaschinen und geringe Margen erfordern von den Lohnunternehmern eine effiziente Auslastung ihres Landmaschinenparks. Um kurze Einsatzzeiten zu erreichen, wie es insbesondere bei der Ernte notwendig ist, werden kurze Fahrzeiten zwischen den Einsatzorten und eine hohe Auslastung der Erntemaschinen, z.B. Feldhäcksler und Mähdreschern, angestrebt. In diesem Beitrag wird der Ernteprozess mit Feldhäckslern und Unterstützungsfahrzeugen (Überlade- und Transportfahrzeuge) untersucht. Dabei muss der Feldhäcksler, wenn nicht genügend Begleitfahrzeuge zur Verfügung stehen, die Ernte auf dem Feld unterbrechen und auf ein Begleitfahrzeug warten, das die geerntete Biomasse aufnehmen kann. Typischerweise werden Teams aus Erntemaschinen und Unterstützungsfahrzeugen vor Beginn des Erntevorgangs zusammengestellt und bleiben in dieser Konstellation, bis alle Felder im Planungszeitraum abgeerntet sind. Im Fokus dieser Studie steht die sich ergebende Zeitersparnis, wenn die Fahrzeuge nicht an ihr Team gebunden sind und somit jedes Feld in einer neuen Konstellation beernten können. In diesem Beitrag werden zwei mathematische Modelle vorgestellt, die den Ernteprozess mit Feldhäckslern, Übergabefahrzeugen und Transportern beschreiben, wobei der Schwerpunkt auf der Auslastung der Feldhäcksler bei fester bzw. variabler Teamzusammensetzung liegt. Diese Modelle werden mittels gemischtganzzahliger Programmierung mit dem Solver Gurobi gelöst

Evaluation of Pulmonary Edema: Stereological versus Gravimetrical Analysis

Assessment of lung edema by gravimetrical analysis is a standard method to evaluate the severity of experimentally induced ischemia/reperfusion (IR) injury. The aim of this study was to compare gravimetrical assessment of pulmonary edema with a stereological approach which allows for qualitative and quantitative distinction between intravascular and edematous fluids by light microscopy. Eight experimental groups which differed in mode of preservation, ischemic storage and pharmacological treatments were studied in an extracorporeal rat lung model. Analysis of the pooled data showed that the wet/dry ratio values mainly reflected the amount of intra-alveolar edema (rs = 0.442; p = 0.0057) but only stereological assessment of edema formation revealed differences depending on the treatment used. Only stereological data correlated significantly with oxygen tension measured at the end of reperfusion (rs = –0.530; p = 0.0009). We conclude that gravimetry is of minor functional importance compared to assessment by stereological methods which prove to be a reliable and efficient tool for the evaluation of IR injury in the different experimental settings.Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich

Off-pump or minimized on-pump coronary surgery - initial experience with Circulating Endothelial Cells (CEC) as a supersensitive marker of tissue damage

Background: Off-pump-coronary-artery-bypass-grafting (OPCAB) and minimized-extracorporeal-circulation (Mini-HLM) have been proposed to avoid harmful effects of cardiopulmonary-bypass (CPB). Controversies exist whether OPCAB is still superior in perioperative outcome. Circulating endothelial cells (CEC) are sensitive markers of endothelial damage and are significantly elevated in conventional-CPB-procedures as compared to Mini-HLM-revascularisation. Therefore, CEC might be of specific value in evaluating effectiveness of Mini-HLM and OPCAB as currently applied less-invasive coronary procedures. Methods: 76 coronary patients were randomly assigned either to OPCAB (n = 34) or to Mini-HLM (ROCsafe (TM), Terumo Inc., n = 42) procedures. Perioperative data, clinical and serological outcome and measurements of CEC-release and parameters of endothelial function (v. Willebrand-Factor, soluble-thrombomodulin) perioperatively (preoperative-baseline, post-Mini-HLM/release of OPCAB-stabilizer, 6 h, 12 h, 24 h and 5 days postoperatively) were obtained and compared by ANOVA models including repeated-measures-analysis. Results: Mean graft-number was 3.06 +/- 0.72 in Mini-HLM-patients and 1.89 +/- 0.74 in OPCAB-patients (p 0.05). CEC-release did not differ between groups (p = 0.274) and was generally within normal limits, Troponin-T levels where not significanty different (p = 0.108). No myocardial infarctions, strokes or deaths occurred, neuron specific enolase (NSE) did not show any differences between groups (p = 0.194). Conclusion: Conceptional advantages of minimized CPB systems (ROCsafe (TM)) result in morbidity and mortality comparable with OPCAB procedures. Mini-HLM therefore minimizes CPB-related systemic and organ injury as demonstrated by low CEC-values which indicates intact endothelial integrity. Furthermore, Mini-HLM combines OPCAB-benefits with low morbidity in high-risk patients while facilitating more complete revascularization in complex patients