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Journal of the American College of Cardiology 08/2014; 64(8):781–783.
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ABSTRACT: Regenerative cell-based therapies are associated with limited myocardial retention of delivered stem cells. The objective of this study is to develop an endocardial delivery system for enhanced cell retention.
Stem cell retention was simulated in silico using 1- and 3-dimensional models of tissue distortion and compliance associated with delivery. Needle designs, predicted to be optimal, were accordingly engineered using nitinol, a nickel and titanium alloy displaying shape memory and superelasticity. Biocompatibility was tested with human mesenchymal stem cells. Experimental validation was performed with species-matched cells directly delivered into Langendorff-perfused porcine hearts or administered percutaneously into the endocardium of infarcted pigs. Cell retention was quantified by flow cytometry and real-time quantitative polymerase chain reaction methodology. Models, computing optimal distribution of distortion calibrated to favor tissue compliance, predicted that a 75°-curved needle featuring small-to-large graded side holes would ensure the highest cell retention profile. In isolated hearts, the nitinol curved needle catheter (C-Cath) design ensured 3-fold superior stem cell retention compared with a standard needle. In the setting of chronic infarction, percutaneous delivery of stem cells with C-Cath yielded a 37.7±7.1% versus 10.0±2.8% retention achieved with a traditional needle without effect on biocompatibility or safety.
Modeling-guided development of a nitinol-based curved needle delivery system with incremental side holes achieved enhanced myocardial stem cell retention.
Circulation Cardiovascular Interventions 12/2013;
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ABSTRACT: Monocyte-platelet aggregates (MPA) are increased in patients with acute coronary syndrome. We investigated whether MPA are associated with the presence of functionally significant coronary stenoses or with coronary arterial endothelial dysfunction. One hundred forty five patients undergoing elective coronary angiography were prospectively enrolled. Functional significance of coronary stenosis was assessed by fractional flow reserve (FFR). Thirty randomly selected patients underwent pacing protocol to evaluate Coronary endothelium-dependent vasomotor function (CVF). Whole blood was drawn to evaluate MPA. In patients with FFR ≤ 0.8 (FFRpos, n = 75), MPA did not significantly differ from FFR >0.8 patients (FFRneg, n = 70) (38.1 % [25.7-56.6] vs 34.0 % [20.5-49.9], p = 0.08). CVF was similar in FFRpos and FFRneg patients (percent vessel diameter change, %VDC = 7.19 % [6.01-10.9] vs 8.0 % [0.81-9.80], p = 0.78). Yet, patients with abnormal CVF showed higher MPA as compared to patients with preserved CVF (28.3 % [28.8-53.4] vs 20.5 % [17.0-32.9], p = 0.01). Moreover, MPA was inversely correlated with %VDC (R (2) = 0.26, p < 0.01). MPA levels are significantly higher in patients with abnormal coronary vasomotor function regardless of the presence of functionally significant coronary stenosis.
Journal of Cardiovascular Translational Research 12/2013;
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