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.
Zimmermann
Wolfram-Hubertus
WH
Institute of Experimental and Clinical Pharmacology, University Medical Center Hamburg-Eppendorf, Germany. w.zimmermann@uke.uni-hamburg.de
Melnychenko
Ivan
I
Wasmeier
Gerald
G
Didié
Michael
M
Naito
Hiroshi
H
Nixdorff
Uwe
U
Hess
Andreas
A
Budinsky
Lubos
L
Brune
Kay
K
Michaelis
Bjela
B
Dhein
Stefan
S
Schwoerer
Alexander
A
Ehmke
Heimo
H
Eschenhagen
Thomas
T
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