Cellular replacement therapy has emerged as a novel strategy for the treatment of heart failure. The aim of our study was to determine the fate of injected mesenchymal stem cells (MSCs) and whole bone marrow (BM) cells in the infarcted heart. MSCs were purified from BM of transgenic mice and characterized using flow cytometry and in vitro differentiation assays. Myocardial infarctions were generated in mice and different cell populations including transgenic MSCs, unfractionated BM cells, or purified hematopoietic progenitors were injected. Encapsulated structures were found in the infarcted areas of a large fraction of hearts after injecting MSCs (22 of 43, 51.2%) and unfractionated BM cells (6 of 46, 13.0%). These formations contained calcifications and/or ossifications. In contrast, no pathological abnormalities were found after injection of purified hematopoietic progenitors ( IntroductionSevere heart failure is caused by an irreversible loss of cardiomyocytes and has a poor prognosis regardless of the underlying disease. 1 Since medical treatment is of only limited help, solid organ transplantation was considered until recently the only effective therapy. However, as organ availability decreases, there is an urgent need for alternative treatments. Studies in mice have suggested that myocardial infarctions can be repaired following transplantation of bone marrow (BM)-derived cells into the lesioned myocardium, either through generation of cardiomyocytes or angiogenesis. 2 An underlying assumption of this approach is that the environment will instruct as well as restrict the developmental fate of adult stem cells after their transplantation (for review see Laflamme and Murry 3 or Murry et al 4 ). However, the original findings in mice have recently been put into question, since we and others have demonstrated that BM-derived hematopoietic cells do not transdifferentiate into cardiomyocytes in the infarcted myocardium. [5][6][7] In this study, we focused on the potential of an enriched population of mesenchymal stem cells (MSCs) that are known to be present in the BM and are multipotent. 8 In contrast to hematopoietic progenitors, MSCs are easy to obtain and to expand in vitro and have therefore emerged as attractive candidates for cellular therapies in heart and other organs. 9,10 However, recent reports have questioned their "transdifferentiation" potential after injection into the myocardium and rather propose benefits via paracrine mechanisms. 11,12 Herein, we investigated and provide novel insights with regard to the fate of enriched populations of BM-derived MSCs as well as whole BM cells comprising both hematopoietic and mesenchymal progenitors after transplantation into the infarcted heart. Materials and methodsAll experiments were approved by the local ethics care committees at Bonn, Cologne, and Lund Universities. Cells for transplantation were isolated from transgenic C57Bl/6 mice expressing enhanced green fluorescent protein (EGFP) under control of the ␤-actin promoter. 13 Cell isolation and cultu...

Ventricular tachyarrhythmias are the main cause of sudden death in patients after myocardial infarction. Here we show that transplantation of embryonic cardiomyocytes (eCMs) in myocardial infarcts protects against the induction of ventricular tachycardia (VT) in mice. Engraftment of eCMs, but not skeletal myoblasts (SMs), bone marrow cells or cardiac myofibroblasts, markedly decreased the incidence of VT induced by in vivo pacing. eCM engraftment results in improved electrical coupling between the surrounding myocardium and the infarct region, and Ca2+ signals from engrafted eCMs expressing a genetically encoded Ca2+ indicator could be entrained during sinoatrial cardiac activation in vivo. eCM grafts also increased conduction velocity and decreased the incidence of conduction block within the infarct. VT protection is critically dependent on expression of the gap-junction protein connexin 43 (Cx43; also known as Gja1): SMs genetically engineered to express Cx43 conferred a similar protection to that of eCMs against induced VT. Thus, engraftment of Cx43-expressing myocytes has the potential to reduce life-threatening post-infarct arrhythmias through the augmentation of intercellular coupling, suggesting autologous strategies for cardiac cell-based therapy.

Interventional radiological procedures have now taken their place alongside conservative treatment and surgery in the management of chylothorax, although they are currently available in only a small number of centers.

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BackgroundAortic stenosis is a frequent valvular disease especially in elderly patients. Catheter-based valve implantation has emerged as a valuable treatment approach for these patients being either at very high risk for conventional surgery or even deemed inoperable. The German Aortic Valve Registry (GARY) provides data on conventional and catheter-based aortic procedures on an all-comers basis.Methods and resultsA total of 13 860 consecutive patients undergoing repair for aortic valve disease [conventional surgery and transvascular (TV) or transapical (TA) catheter-based techniques] have been enrolled in this registry during 2011 and baseline, procedural, and outcome data have been acquired. The registry summarizes the results of 6523 conventional aortic valve replacements without (AVR) and 3464 with concomitant coronary bypass surgery (AVR + CABG) as well as 2695 TV AVI and 1181 TA interventions (TA AVI). Patients undergoing catheter-based techniques were significantly older and had higher risk profiles. The stroke rate was low in all groups with 1.3% (AVR), 1.9% (AVR + CABG), 1.7% (TV AVI), and 2.3% (TA AVI). The in-hospital mortality was 2.1% (AVR) and 4.5% (AVR + CABG) for patients undergoing conventional surgery, and 5.1% (TV AVI) and AVI 7.7% (TA AVI).ConclusionThe in-hospital outcome results of this registry show that conventional surgery yields excellent results in all risk groups and that catheter-based aortic valve replacements is an alternative to conventional surgery in high risk and elderly patients.