Cardiac Tissue Engineering in an In Vivo Vascularized Chamber

• DOI: 10.1161/circulationaha.106.657379
• Publication Date: 2007-01-03T02:57:14Z
• Authors: Andrew N. Morritt; Susan K. Bortolotto; Rodney J. Dilley; XiaoLian Han; Andrew R. Kompa; David McCombe; Christine E. Wright; Silviu Itescu; James A. Angus; Wayne A. Morrison
• Keywords: Desmin; Immunostaining; Cardiac muscle; Cardiac Ventricle

Background— Cardiac tissue engineering offers the prospect of a novel treatment for acquired or congenital heart defects. We have created vascularized pieces beating cardiac muscle in rat that are as thick adult right ventricle wall. Method and Results— Neonatal cardiomyocytes Matrigel were implanted with an arteriovenous blood vessel loop into 0.5-mL patented tissue-engineering chamber, located subcutaneously groin. Chambers harvested 1, 4, 10 weeks after insertion. At 4 weeks, all constructs grew chambers contracted spontaneously. Immunostaining α-sarcomeric actin, troponin, desmin showed differentiated present at time points formed network interconnected cells within collagenous extracellular matrix. Constructs extensively vascularized. The maximum thickness generated was 1983 μm. Cardiomyocytes increased size from 1 to positive proliferation markers Ki67 PCNA. Connexin-43 stain indicated gap junctions between weeks. Echocardiograms performed construct spontaneously vivo. In vitro organ bath experiments typical length-tension relationship, ability be paced electrical field pulses up 3 Hz, chronotropy norepinephrine, inotropy response calcium. Conclusion— summary, use chamber allowed generation 3-dimensional mass neonatal cardiomyocytes. Further development this model will increase potential provide suitable replacement tissues