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

Transapical aortic valve implantation with a self-expanding anatomically oriented valve

Aims The Medtronic Engager™ aortic valve bioprosthesis is a self-expanding valve with support arms facilitating anatomically correct positioning and axial fixation. Valve leaflets, made of bovine pericardium, are mounted on a Nitinol frame. Here, we report the first in man study with this new implant (Trial Identifier NCT00677638). Methods and results Thirty patients (mean age 83.4 ± 3.8 years; 83% female) with tricuspid aortic valve stenosis were included in the study. Mean logistic EuroSCORE was 23.4 ± 11.9. Mean aortic annulus diameter was 21.8 ± 1.4 mm. For this study, the Engager was available in only one size (23 mm), to fit aortic annuli of 19-23 mm. Standard transapical valve implantation was performed using predilation of the aortic valve and rapid ventricular pacing during ballon valvuloplasty and most valve deployments. Accurate valve placement was achieved in 29/30 cases (97%). Post-implant peak-to-peak gradient was 13.3 ± 9.3 mmHg. In 80% of the patients, no more than grade I paravalvular leakage was observed, in 13% grades I-II and in 3% grade II. Three patients (10%) required permanent pacemaker implantation for higher-degree or complete atrioventricular block. Four dissections (13%) occurred during positioning of the valve and were treated surgically in three cases. Thirty-day and in-hospital mortality were 20% and 23%, respectively, and 6-month survival was 56.7%. No structural failure occurred for up to 1 year. Conclusion This series established the feasibility of implanting a novel self-expanding transapical aortic valve prosthesis predictably into an anatomically correct position. Observed complications led to complete redesign of the delivery system for upcoming clinical studies with the goal of establishing safety and performanc

Transfemoral transcatheter aortic valve implantation in a patient with multiple endovascular aortic stents – a case report

Background: In patients undergoing transfemoral transcatheter aortic valve implantation, previous endovascular interventions bear a risk for the valve frame to get stucked to the aortic stents. Case Presentation: We report on a 75-year-old frail patient with severe aortic stenosis and a rapid increase of an infra-renal aneurysm. He had a history of multiple endovascular interventions on the aorta. Due to his frail preoperative status we decided to perform a transfemoral transcatheter aortic valve implantation in combination with a simultaneous surgical abdominal aneurysm repair. To allow an atraumatic passage of the Edwards SAPIEN 3 valve across the endovascular stents we used a special technique. Conclusions: The transfemoral approach in patients with previous endovascular stenting can be performed successfully by a partial inflation of the distal balloon

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

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The European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery:third report

OBJECTIVES: In the third report of the European Registry for Patients with Mechanical Circulatory Support of the European Association for Cardio-Thoracic Surgery, outcomes of patients receiving mechanical circulatory support are reviewed in relation to implant era. METHODS: Procedures in adult patients (January 2011-June 2020) were included. Patients from centres with 3 months). Risk factors for death were explored using univariable Cox regression with a stepwise time-varying hazard ratio (3 months). RESULTS: In total, 4834 procedures in 4486 individual patients (72 hospitals) were included, with a median follow-up of 1.1 (interquartile range: 0.3-2.6) years. The annual number of implants (range: 346-600) did not significantly change (P = 0.41). Both Interagency Registry for Mechanically Assisted Circulatory Support class (classes 4-7: 23, 25 and 33%; P 3 months: 0.45). Bilirubin and creatinine levels were significant risk factors in the early phase but not in the late phase after the implant. CONCLUSIONS: In its 10 years of existence, EUROMACS has become a point of reference enabling benchmarking and outcome monitoring. Patient characteristics and outcomes changed between implant eras. In addition, both occurrence of outcomes and risk factor weights are time dependent

Umzug Uni Klinik am 25.03.2004

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