Cardiac conduction through engineered tissue.
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 lec-tin demonstrated that implanted tissues became vascularized and immunostaining verified the presence of proteins important in electromechanical integration of myogenic cells with surrounding re-cipient 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.
Choi
Yeong-Hoon
YH
Department of Cardiac Surgery, Children's Hospital Boston, Boston, MA 02115, USA.
Stamm
Christof
C
Hammer
Peter E
PE
Kwaku
Kevin F
KF
Marler
Jennifer J
JJ
Friehs
Ingeborg
I
Jones
Mara
M
Rader
Christine M
CM
Roy
Nathalie
N
Eddy
Mau-Thek
MT
Triedman
John K
JK
Walsh
Edward P
EP
McGowan
Francis X
FX
del Nido
Pedro J
PJ
Cowan
Douglas B
DB
D000818:Animals; D001283:Atrioventricular Node / Q000502:physiology; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D017690:Cell Transplantation; D017630:Connexins; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D046529:Microscopy, Electron, Transmission; D032342:Muscle Cells / Q000166:cytology* / Q000637:transplantation*; D018482:Muscle, Skeletal / Q000098:blood supply / Q000166:cytology* / Q000502:physiology; D016133:Polymerase Chain Reaction; D051381:Rats; D011917:Rats, Inbred Lew; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D023822:Tissue Engineering
D017630:Connexins