Pulsatile myocardial tubes fabricated with cell sheet engineering.
BACKGROUND
Tissue engineering approaches involving the direct transplantation of cardiac patches have received significant attention as alternative methods for the treatment of damaged hearts. In contrast, we used cardiomyocyte sheets harvested from temperature-responsive culture dishes to create pulsatile myocardial tubes and examined their in vivo function and survival.


RESULTS
Neonatal rat cardiomyocyte sheets were sequentially wrapped around a resected adult rat thoracic aorta and transplanted in place of the abdominal aorta of athymic rats (n=17). Four weeks after transplantation, the myocardial tubes demonstrated spontaneous and synchronous pulsations independent of the host heartbeat. Independent graft pressures with a magnitude of 5.9+/-1.7 mm Hg due to their independent pulsations were also observed (n=4). Additionally, histological examination and transmission electron microscopy indicated that the beating tubes were composed of cardiac tissues that resemble the native heart. Finally, when myocardial tubes used for aortic replacement were compared with grafts implanted in the abdominal cavity (n=7), we observed significantly increased tissue thickness, as well as expression of brain natriuretic peptide, myosin heavy chain-alpha, and myosin heavy chain-beta.


CONCLUSIONS
Functional myocardial tubes that have the potential for circulatory support can be created with cell sheet engineering. These results also suggest that pulsation due to host blood flow within the lumen of the myocardial tubes has a profound effect on stimulating cardiomyocyte hypertrophy and growth. These results demonstrate a novel approach for the future development of engineered cardiac tissues with the ability for independent cardiac assistance.
Sekine
Hidekazu
H
Institute of Advanced Biomedical Engineering and Science, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.
Shimizu
Tatsuya
T
Yang
Joseph
J
Kobayashi
Eiji
E
Okano
Teruo
T
D000818:Animals; D000831:Animals, Newborn; D001012:Aorta, Abdominal / Q000601:surgery*; D001013:Aorta, Thoracic / Q000637:transplantation; D018929:Cell Culture Techniques / Q000295:instrumentation; D002478:Cells, Cultured / Q000637:transplantation; D004562:Electrocardiography; D020869:Gene Expression Profiling; D008866:Microsurgery; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D032383:Myocytes, Cardiac / Q000166:cytology / Q000378:metabolism / Q000637:transplantation*; D018995:Myosin Heavy Chains / Q000096:biosynthesis / Q000235:genetics; D020097:Natriuretic Peptide, Brain / Q000096:biosynthesis / Q000235:genetics; D009924:Organ Culture Techniques; D051381:Rats; D011923:Rats, Nude; D017208:Rats, Wistar; D013696:Temperature; D023822:Tissue Engineering / Q000379:methods*
C000594638:MYH7 protein, rat; C495963:natriuretic peptide precursor type B, rat; D020097:Natriuretic Peptide, Brain; D018995:Myosin Heavy Chains