X-Message-Number: 29519
From: David Stodolsky <>
Subject: Engineered heart tissue
Date: Sun, 20 May 2007 21:15:39 +0200

Abstract from Thomas Eschenhagen, Institute of Pharmacology,  
University Medical Center Hamburg-Eppendorf, Germany

Over the past decade we have developed methods to generate
spontaneously and synchronously beating tissue equivalents from
neonatal rat heart cells in the culture dish. These tissue equivalents
display the key morphological and functional features of intact
myocardium and have been termed engineered heart tissue (EHT). To
generate EHTs, heart cells are mixed with freshly neutralized, liquid
collagen I, matrigel and growth supplements and grown in a circular
casting mold around a central cylinder, which subjects the cells
to a continuous mechanical load. This process is enforced by cyclic
mechanical stretch. We use EHT mainly for two purposes, as a test
bed for the effects of pharmacological or genetic manipulations and
for cardiac repair. As a cell culture model, EHTs compare with standard
2D monolayer cultures of neonatal rat cardiac myocytes and
freshly isolated adult cardiac myocytes. Advantages of EHTs are
their functional similarities with intact heart muscles, the ability to
easily measure force of contraction under mechanical load, the  
possibility
to transfect cardiac myocytes inside EHTs with adenovirus
at high efficiency and the reproducibility in large series. A  
disadvantage
is that contractile function as measured at the end of the culture
period also integrates influences on tissue development,
cell cellconnections,
extracellular matrix production and on non-myocytes.
At present we are working on downscaling the EHT method to a 96-
well format for screening purposes. To use EHTs for cardiac repair
we created multi-looped EHTs from five circular EHTs large enough
to cover the infarct scar 14 days after coronary artery ligation in  
rats.
EHTs survived and formed a layer of muscle tissue on top of the
infarct scar. EHTs restored undelayed anterograde impulse propagation
over the scar, prevented further ventricular dilatation, normalized
enddiastolic pressure and relaxation, and partly restored contraction
of the scar. Thus, the study provides evidence that implanting EHTs
onto infarcted hearts can improve cardiac contractile function after
myocardial infarction.


David Stodolsky    Skype: davidstodolsky

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