Engineered heart tissue: A novel tool to study the ischemic changes of the heart in vitro

Rajesh G. Katare, Motonori Ando, Yoshihiko Kakinuma, Takayuki Sato

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Background: Understanding 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 Findings: EHT 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/Significance: Under hypoxic conditions, the EHT responds similarly to the adult myocardium, thus making EHT a promising material for the study of cardiac functions in vitro.

Original languageEnglish
Article numbere9275
JournalPLoS One
Volume5
Issue number2
DOIs
Publication statusPublished - Feb 17 2010
Externally publishedYes

Fingerprint

heart
Tissue
Stretching
connexins
Protective Agents
Connexin 43
hypoxia
tissues
In Vitro Techniques
Theoretical Models
Optical Devices
cyclosporine
dephosphorylation
disease prevention
acetylcholine
cardiac output
action potentials
ischemia
myocardium
Cardiac Myocytes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Engineered heart tissue : A novel tool to study the ischemic changes of the heart in vitro. / Katare, Rajesh G.; Ando, Motonori; Kakinuma, Yoshihiko; Sato, Takayuki.

In: PLoS One, Vol. 5, No. 2, e9275, 17.02.2010.

Research output: Contribution to journalArticle

Katare, Rajesh G. ; Ando, Motonori ; Kakinuma, Yoshihiko ; Sato, Takayuki. / Engineered heart tissue : A novel tool to study the ischemic changes of the heart in vitro. In: PLoS One. 2010 ; Vol. 5, No. 2.
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