Cardiac Conduction through Engineered Tissue
| Autor: | Mau-Thek Eddy, Douglas B. Cowan, Francis X. McGowan, Edward P. Walsh, Peter E. Hammer, Christine M. Rader, Kevin F. Kwaku, Christof Stamm, Nathalie Roy, Jennifer J. Marler, John K. Triedman, Yeong-Hoon Choi, Mara Jones, Ingeborg Friehs, Pedro J. del Nido |
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| Rok vydání: | 2006 |
| Předmět: |
Pathology
medicine.medical_specialty Cell Transplantation Immunoblotting Cell Communication In situ hybridization Biology Polymerase Chain Reaction Connexins Pathology and Forensic Medicine Microscopy Electron Transmission Tissue engineering Heart Conduction System Cardiac conduction medicine Animals Myocyte Muscle Skeletal In Situ Hybridization Fluorescence Electronic pacemaker Muscle Cells Tissue Engineering Stem Cells Cell Differentiation Heart Immunohistochemistry Atrioventricular node Rats medicine.anatomical_structure Rats Inbred Lew Atrioventricular Node Implant Electrical conduction system of the heart Regular Articles |
| Zdroj: | The American Journal of Pathology. 169:72-85 |
| ISSN: | 0002-9440 |
| DOI: | 10.2353/ajpath.2006.051163 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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