Cardiac conduction through engineered tissue

被引:55
作者
Choi, YH
Stamm, C
Hammer, PE
Kwaku, KF
Marler, JJ
Friehs, I
Jones, M
Rader, CM
Roy, N
Eddy, MT
Triedman, JK
Walsh, EP
McGowan, FX
del Nido, PJ
Cowan, DB
机构
[1] Childrens Hosp, Dept Anesthesiol, Boston, MA 02115 USA
[2] Childrens Hosp, Dept Cardiac Surg, Boston, MA 02115 USA
[3] Childrens Hosp, Dept Surg, Boston, MA 02115 USA
[4] Childrens Hosp, Dept Cardiol, Boston, MA 02115 USA
[5] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Cardiovasc, Boston, MA USA
关键词
D O I
10.2353/ajpath.2006.051163
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
In children, interruption of cardiac atrioventricular (AV) electrical conduction can result from congenital defects, surgical interventions, and maternal autoimmune diseases during pregnancy. Complete AV conduction block is typically treated by implanting an electronic pacemaker device, although long-term pacing therapy in pediatric patients has significant complications. As a first step toward developing a substitute treatment, we implanted engineered tissue constructs in rat hearts to create an alternative AV conduction pathway. We found that skeletal muscle-derived cells in the constructs exhibited sustained electrical coupling through persistent expression and function of gap junction proteins. Using fluorescence in situ hybridization and polymerase chain reaction analyses, myogenic cells in the constructs were shown to survive in the AV groove of implanted hearts for the duration of the animal's natural life. Perfusion of hearts with fluorescently labeled lectin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding recipient rat cardiomyocytes. Finally, using optical mapping and electrophysiological analyses, we provide evidence of permanent AV conduction through the implant in one-third of recipient animals. Our experiments provide a proof-of-principle that engineered tissue constructs can function as an electrical conduit and, ultimately, may offer a substitute treatment to conventional pacing therapy.
引用
收藏
页码:72 / 85
页数:14
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