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Injectable Matrix Bioscaffolds Improve LV Function and Stimulate Cardiomyocyte Regeneration in Infarcted Hearts
W. Douglas Boyd1, Robert G. Matheny2, Anna M. Fallon2, Dongming Hou3, Stephen Frohwein4, Marc Gerdisch5.
1University of California, Sacramento, CA, USA, 2CorMatrix Cardiovascular, Atlanta, GA, USA, 3St. Joseph Translational Research Institute, Atlanta, GA, USA, 4St. Josephs Hospital, Atlanta, CA, USA, 5St. Francis Hospital, Indianapolis, IN, USA.
OBJECTIVE:
After myocardial infarction (MI), necrosis in the ischemic region causes negative remodeling that leads to left ventricular dysfunction, arrhythmias and subsequent congestive heart failure (CHF). Regenerative therapies to treat CHF must provide mechanical support, limit apoptosis, promote angiogenesis and restore cardiomyocytes. CorMatrix injectable extracellular matrix (I-ECM) is manufactured from decellularized porcine small intestine submucosa (SIS) containing glycoproteins, glycosaminoglycans, and growth factors. SIS scaffolds have demonstrated chemotactic properties, and in a rat MI model, I-ECM recruited c-kit+ cells to sites of ischemic damage resulting in improved functional endpoints including ejection fraction (EF). The synergistic effects of I-ECM include mechanically maintaining normal myocardial physiology while recruiting c-kit+ cells to the site to become cardiomyocytes.The objective of the current study was to determine if injectable extracellular matrix bioscaffolds can improve LV function and regenerate myocytes in a large-animal model of chronic ischemic CH.
METHODS:
A chronic study using a porcine MI model (n=9, 5 test, 4 control) evaluated therapeutic effects of I-ECM injected 2-3 months after negative remodelling had occurred. The left anterior descending coronary artery was occluded with collagen to induce ischemic damage to the left ventricle and septum. An MRI was performed 60-81 days post infarction. The animals then underwent either a sham procedure or therapeutic I-ECM injections. Restudy was performed at 5 and 8 months post-injection. Ventricular function was assessed via MRI, and the infarct area was evaluated histologically to show collagen distribution and demonstrate the presence of cardiomyocytes.
RESULTS:
EF was significantly improved (p<0.05) compared to untreated controls 5 and 8 months post I-ECM, and end systolic volume (ESV) was significantly improved (p<0.05) compared to untreated controls 8 months post I-ECM. Control EFs were 37.9±2.6% and 42.1±5.4% compared to 46.8±6.5% and 49.3±3.8% after I-ECM therapy, at 5 and 8 mos post treatment, respectively. Control ESV was 40.2±8.2ml compared to 27.4±7.9ml 8 mos post I-ECM Histology demonstrated arteriogenesis and cells surrounding the degrading I-ECM. Cardiomyocytes were seen in the I-ECM suggesting regeneration of new cardiac muscle.
CONCLUSIONS:
Surgical delivery of injectable ECM bioscaffolds significantly improves chronic CHF by positive remodeling and may facilitate cardiac regeneration.
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