In Vitro Human Engineered Myocardium: A Study into both Pathological and Physiological Hypertrophy

• Main Author: Miklas, Jason
• Other Authors: Radisic, Milica
• Language: en_ca
• Published: 2013
• Subjects: Cardiomyocyte; Stem Cells; Tissue Engineering; Disease Modelling; 0541
• Online Access: http://hdl.handle.net/1807/43241

The ability to generate cardiomyocytes from either embryonic stem cells or induced pluripotent stem cells provides an unprecedented opportunity to establish human in vitro models of cardiovascular disease as well as to develop platforms for the testing of novel cardiac therapeutics. We designed two different platforms, a biowire platform and post deflection platform, to generate engineered heart tissues (EHTs) to study a fundamental process in cardiomyocytes: hypertrophy. Both pathological and physiological hypertrophy was studied in order to garner a better understanding of each process. Physiological hypertrophy characteristics were observed using the biowire platform seen in improved myofibril alignment and downregulation of fetal genes. When electrical stimulation was added, a rate dependent effect on sarcomere maturation was observed by the increased frequency of I-bands and H-zones. Certain hallmark features of pathological hypertrophy, such as upregulation of brain natriuretic peptide and sarcomere structure breakdown, were recapitulated when EHTs were treated with isoproterenol.