ECENT CLINICAL TRIALS SUGgest that bone marrowderived cell preparations, including mononuclear cells 1-5 and mesenchymal stem cells (MSCs), [6][7][8] can ameliorate left ventricular (LV) remodeling in patients with acute 1,3,8 and chronic 2,4,6,9 ischemic cardiomyopathy (ICM). An important issue in this new field is whether a certain cellular constituent Author Affiliations are listed at the end of this article.

To demonstrate the safety of transendocardial stem cell injection (TESI) with autologous MSCs and BMCs in patients with ICM.• To assess prespecified outcomes of efficacy.

Rationale Transcatheter, intramyocardial injections of bone marrow derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy. Objective We used cardiac magnetic resonance imaging (CMR) in patients with LV dysfunction related to remote myocardial infarction (MI) to test the hypothesis that bone marrow progenitor cell injection cause functional recovery of scarred myocardium and reverse remodeling. Methods and Results Eight patients (age 57.2±13.3) received transendocardial, intramyocardial injection of autologous bone marrow progenitor cells (mononuclear or mesenchymal stem cells) in LV scar and border zone. All patients tolerated the procedure with no serious adverse events. CMR at 1-year demonstrated a decrease in end-diastolic volume (208.7±20.4 vs. 167.4±7.32mL; p=0.03), a trend towards decreased end-systolic volume (142.4±16.5 vs. 107.6±7.4mL; p=0.06), decreased infarct size (p<0.05), and improved regional LV function by peak Ecc in the treated infarct zone (-8.1±1.0 vs. -11.4±1.3; p=0.04). Improvements in regional function were evident at 3 months, while the changes in chamber dimensions were not significant until 6 months. Improved regional function in the infarct zone strongly correlated with reduction of EDV (r2=0.69, p=0.04) and ESV (r2=0.83, p=0.01). Conclusions These data suggest that transcatheter, intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar and these changes predict subsequent reverse remodeling. The findings support the potential clinical benefits of this new treatment strategy and ongoing randomized clinical trials.

Specimens of bovine, rabbit, and human corneas were systematically tested in uniaxial tension to experimentally determine their effective nonlinear stress-strain relations, and hysteresis. Cyclic tensile tests were performed over the physiologic load range of the cornea, up to a maximum of 10 percent strain beyond slack strain. Dimensional changes to corneal test specimens, due to varying laboratory environmental conditions, were also assessed. The measured stress-strain data was found to closely fit exponential power function relations typical of collagenous tissues when appropriate account was taken of specimen slack strain. These constitutive relations are very similar for rabbit, human and bovine corneas; there was no significant difference between the species after preconditioning by one cycle. The uniaxial stress strain curves for all species behave similarly in that their tangent moduli increase at high loads and decrease at low loads as a function of cycling. In the bovine and rabbit data, there is a general trend towards more elastic behavior from the first to second cycles, but there is little variation in these parameters from the second to third cycles. In comparison, the human data demonstrates relatively little change between cycles. Increases in width of corneal test specimens, up to a maximum of 2 percent were found to occur under 95 percent relative humidity test conditions over 10 minutes elapsed time test periods, while specimens which were exposed to normal laboratory conditions (45 percent RH) were found to shrink in width up to a maximum of 9.5 percent over the same elapsed time period. The thickness of the test specimens were observed to decrease by 3 percent in 95 percent relative humidity and by 12 percent in 45 percent relative humidity over the same elapsed time period.

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