Non-human primate studies for cardiomyocyte transplantation—ready for translation?

Non-human primates (NHP) are valuable models for late translational pre-clinical studies, often seen as a last step before clinical application. The unique similarity between NHPs and humans is often the subject of ethical concerns. However, it is precisely this analogy in anatomy, physiology, and the immune system that narrows the translational gap to other animal models in the cardiovascular field. Cell and gene therapy approaches are two dominant strategies investigated in the research field of cardiac regeneration. Focusing on the cell therapy approach, several xeno- and allogeneic cell transplantation studies with a translational motivation have been realized in macaque species. This is based on the pressing need for novel therapeutic options for heart failure patients. Stem cell-based remuscularization of the injured heart can be achieved via direct injection of cardiomyocytes (CMs) or patch application. Both CM delivery approaches are in the late preclinical stage, and the first clinical trials have started. However, are we already ready for the clinical area? The present review concentrates on CM transplantation studies conducted in NHPs, discusses the main sources and discoveries, and provides a perspective about human translation

A Survey of the Galactic Plane for 6.7-GHz Methanol Masers I: l = 325.0 - 335.0 ; b = -0.53 - 0.53

We report the results of the first complete survey of an area of the Galactic Plane for maser emission from the 6.7-GHz transition of methanol. The survey covers a 10.6-square-degree region of the Galactic Plane in the longitude range 325-335 degrees and latitude range -0.53-0.53 degrees. The survey is sensitive to masers with a peak flux density greater than approximately 2.6 Jy. The weakest maser detected has a peak flux density of 2.3 Jy and the strongest a peak flux density of 425 Jy. We detected a total of 50 distinct masers, 26 of which are new detections. We show that many 6.7-GHz methanol masers are not associated with IRAS sources, and that some are associated with sources that have colours differing from those of a typical ultra-compact HII region (UCHII). We estimate that the number of UCHII regions in the Galaxy is significantly more than suggested by IRAS-based estimates, possibly by more than a factor of two.Comment: 19 pages including 4 figures, using LaTeX formatted with mn.sty, accepted for publication in MNRA

Quantification of diastolic dysfunction via the age dependence of diastolic function — Impact of insulin resistance with and without type 2 diabetes

AbstractBackgroundThe alarming prevalence of heart failure with preserved ejection fraction requires quantification of diastolic dysfunction (DDF). Myocardial diastolic velocity E′ implies that age is the most important determinant. We tested the hypothesis that age allows for quantification of DDF and assessment of the structural and metabolic determinants in patients with and without type 2 diabetes (D).MethodsThis prospective, cross-sectional study assessed cardiovascular, metabolic and ultrasound data in 409 consecutive patients (Diabetes Center, Bogenhausen-Munich) between 20 and 90years without known cardiac disease and either with (n=204) or without D but with common prevalence of cardiovascular risk factors, including a subgroup of healthy individuals (H, n=94).ResultsIn H, E′ related to age as: E′norm=−0.163∗years+19.69 (R2=0.77, p<0.0001). According to this 1% reduction by annual physiologic aging, DDF was quantitated as E′−E′ norm. Compared to nondiabetics, D patients were older, had greater BMI, lower E′, more cardiovascular risk and greater DDF. In nondiabetics, grading of DDF by E−E′norm correlated with grading by filling pressure E/E′. Determinants of DDF by multivariate analysis included pulse wave velocity, diastolic blood pressure and the triglyceride/HDL ratio (a marker of insulin resistance) in nondiabetics and in D the same risk factors in reverse sequence and heart rate. Neither left atrial size nor left ventricular mass had significant impact.ConclusionsThe physiological impact of age on myocardial function consists of a 1% annual reduction in E′ and enables precise quantification of diastolic dysfunction thereby unmasking the importance of metabolic risk for DDF