Engineered heart tissue grafts improve systolic and diastolic function in infarcted rat hearts.
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.
Institute of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Germany. w.zimmermann@uke.uni-hamburg.de
Wolfram-Hubertus
WH
Zimmermann
Ivan
I
Melnychenko
Gerald
G
Wasmeier
Michael
M
Didié
Hiroshi
H
Naito
Uwe
U
Nixdorff
Andreas
A
Hess
Lubos
L
Budinsky
Kay
K
Brune
Bjela
B
Michaelis
Stefan
S
Dhein
Alexander
A
Schwoerer
Heimo
H
Ehmke
Thomas
T
Eschenhagen
D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography; D004558:Electric Stimulation; D005456:Fluorescent Dyes; D006321:Heart / Q000187:drug effects; D016027:Heart Transplantation / Q000379:methods*; D007211:Indoles; D007328:Insulin / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008279:Magnetic Resonance Imaging; D008297:Male; D018613:Microscopy, Confocal; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000209:etiology / Q000473:pathology*; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000502:physiology; D010100:Oxygen / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013599:Systole; D013997:Time Factors; D023822:Tissue Engineering / Q000379:methods*; D019737:Transplants; D016277:Ventricular Function, Left
D005456:Fluorescent Dyes; D007211:Indoles; D007328:Insulin; C007293:DAPI; D010100:Oxygen; D002118:Calcium