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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Implantable electrical conductor wires and coils of MP35N and drawn MP35N tube filled with a silver core (DFT) were tested in rotary bending to evaluate fatigue characteristics and failure mechanisms. Detailed stress analysis enabled evaluation of helical coil fatigue in bending with respect to theoretical stress. The relations between the maximum cyclic stress (S) and the cycles to failure (N) were obtained by introducing cyclic stresses on over 600 samples. Microscopic evaluation using scanning electron microscopy was performed to identify failure mechanisms. The results show that the stress analysis presented is a viable means for assessing the stress state in a composite coil structure in rotary loop testing, comparable S-N fatigue data sets for MP35N and DFT conductors are not consistently significantly different, S-N relationships for coils and wires of the MP35N and DFT appear to lie on the same curves, and failures of all sample types initiate on the outside surface of the wire. Differences in crack propagation and final fracture are shown as a function of sample type and cyclic stress.

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Rationale Transendocardial Stem Cell Injection (TESI) with mesenchymal stem cells improves remodeling in chronic ischemic cardiomyopathy, but the impact of the injection site remains unknown. Objective To address whether TESI exerts its effects at the site of injection only or also in remote areas, we hypothesized that segmental myocardial scar and segmental ejection fraction improve to a greater extent in injected than in non-injected segments. Methods and Results Biplane ventriculographic and endocardial tracings were recorded. TESI was guided to 10 sites in infarct-border zones. Sites were mapped according to the 17-myocardial segment model. As a result, 510 segments were analyzed in 30 patients before and 13-months after TESI. Segmental early enhancement defect (SEED, a measure of scar size) was reduced by TESI in both injected (−43.7±4.4%, n=95, p<0.01) and non-injected segments (−25.1±7.8%, n=148, p<0.001; between group comparison p<0.05). Conversely, segmental ejection fraction (SEF, a measure of contractility) improved in injected scar segments (19.9±3.3 to 26.3±3.5%, p=0.003) but not in non-injected scar segments (21.3±2.6 to 23.5±3.2%, p=0.20, between group comparison p<0.05). In the subgroup of scar segments with baseline SEF<20%, the SEF improvement was even greater in injected segments (12.1±1.2% to 19.9±2.7%, n=18, p=0.003) vs. non-injected segments (13.3±1.3% to 16.1±2.1%, n=15, p=0.05; between group comparison p<0.05). Conclusions These findings illustrate a dichotomy in regional responses to TESI. Although scar reduction was evident at the site of TESI and remotely, ventricular functional responses occurred preferentially at the sites of TESI. Furthermore, improvement was greatest when segmental left ventricular dysfunction was severe.