Nature Medicine
- 12, 452 - 458 (2006)
Published online: 2 April 2006; | doi:10.1038/nm1394
Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat heartsWolfram-Hubertus Zimmermann1, 6, Ivan Melnychenko1, 6, Gerald Wasmeier2, Michael Didié1, Hiroshi Naito1, Uwe Nixdorff2, Andreas Hess3, Lubos Budinsky3, Kay Brune3, Bjela Michaelis4, Stefan Dhein4, Alexander Schwoerer5, Heimo Ehmke5 & Thomas Eschenhagen11
Institute of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Martinistra e 52, 20246 Hamburg, Germany. 2
Medical Clinic II, Friedrich-Alexander-University of Erlangen-Nuremberg, Ulmenweg 18, 91054 Erlangen, Germany. 3
Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University of Erlangen-Nuremberg, Fahrstrae 17, 91054 Erlangen, Germany. 4
Heart Center, Department of Cardiac Surgery, University of Leipzig, Strümpellstrae 39, 04289 Leipzig, Germany. 5
Institute of Vegetative Physiology and Pathophysiology, University Medical Center Hamburg-Eppendorf, Martinistrae 52, 20246 Hamburg, Germany. 6
These authors contributed equally to this work.
Correspondence should be addressed to Thomas Eschenhagen t.eschenhagen@uke.uni-hamburg.de or Wolfram-Hubertus Zimmermann w.zimmermann@uke.uni-hamburg.de The concept of regenerating diseased myocardium by implantation of tissue-engineered heart muscle is intriguing, but convincing evidence is lacking that heart tissues can be generated at a size and with contractile properties that would lend considerable support to failing hearts. Here we created large (thickness/diameter, 1–4 mm/15 mm), force-generating engineered heart tissue from neonatal rat heart cells. Engineered heart tissue formed thick cardiac muscle layers when implanted on myocardial infarcts in immune-suppressed rats. When evaluated 28 d later, engineered heart tissue showed undelayed electrical coupling to the native myocardium without evidence of arrhythmia induction. Moreover, engineered heart tissue prevented further dilation, induced systolic wall thickening of infarcted myocardial segments and improved fractional area shortening of infarcted hearts compared to controls (sham operation and noncontractile constructs). Thus, our study provides evidence that large contractile cardiac tissue grafts can be constructed in vitro, can survive after implantation and can support contractile function of infarcted hearts.
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