Abstract
BackgroundUnderstanding the basic mechanisms and prevention of any disease pattern lies mainly on development of a successful experimental model. Recently, engineered heart tissue (EHT) has been demonstrated to be a useful tool in experimental transplantation. Here, we demonstrate a novel function for the spontaneously contracting EHT as an experimental model in studying the acute ischemia-induced changes in vitro.Methodology/Principal FindingsEHT was constructed by mixing cardiomyocytes isolated from the neonatal rats and cultured in a ring-shaped scaffold for five days. This was followed by mechanical stretching of the EHT for another one week under incubation. Fully developed EHT was subjected to hypoxia with 1% O2 for 6 hours after treating them with cell protective agents such as cyclosporine A (CsA) and acetylcholine (ACh). During culture, EHT started to show spontaneous contractions that became more synchronous following mechanical stretching. This was confirmed by the increased expression of gap junctional protein connexin 43 and improved action potential recordings using an optical mapping system after mechanical stretching. When subjected to hypoxia, EHT demonstrated conduction defects, dephosphorylation of connexin-43, and down-regulation of cell survival proteins identical to the adult heart. These effects were inhibited by treating the EHT with cell protective agents.Conclusions/SignificanceUnder hypoxic conditions, the EHT responds similarly to the adult myocardium, thus making EHT a promising material for the study of cardiac functions in vitro.
Highlights
Understanding the basic mechanisms and prevention of any disease pattern lies mainly on development of a successful experimental model
While all the studies have used engineered heart tissue (EHT) as a therapeutic tool, it not known if EHT can replace the whole heart to study the characteristics of cardiovascular diseases in vitro, Zimmermann and colleagues suggested that EHT could become a promising material to study cardiac functions in vitro [4]
In this study, using advanced techniques of optical mapping along with other conventional techniques, we demonstrate that EHT responds similar to the whole heart under basal and stress conditions
Summary
Understanding the basic mechanisms and prevention of any disease pattern lies mainly on development of a successful experimental model. While all the studies have used EHT as a therapeutic tool, it not known if EHT can replace the whole heart to study the characteristics of cardiovascular diseases in vitro, Zimmermann and colleagues suggested that EHT could become a promising material to study cardiac functions in vitro [4]. Recent development of vascularized EHT [7,8,9] further supports our hypothesis that EHT could become a replacement for whole heart studies under in vitro circumstances. Engineered heart tissue (EHT) has been demonstrated to be a useful tool in experimental transplantation. We demonstrate a novel function for the spontaneously contracting EHT as an experimental model in studying the acute ischemia-induced changes in vitro
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