• Klaus Neef, Yeong-Hoon Choi, Sureshkumar Perumal Srinivasan, Philipp Treskes, Douglas B Cowan, Christof Stamm, Martin Rubach, Roland Adelmann, Thorsten Wittwer, and Thorsten Wahlers.
• Department of Cardiac and Thoracic Surgery, Heart Center of the University, University of Cologne, Cologne, Germany.
• J. Thorac. Cardiovasc. Surg.. 2012 Nov 1;144(5):1176-1184.e1.

ObjectiveThe effect of mechanical preconditioning on skeletal myoblasts in engineered tissue constructs was investigated to resolve issues associated with conduction block between skeletal myoblast cells and cardiomyocytes.MethodsMurine skeletal myoblasts were used to generate engineered tissue constructs with or without application of mechanical strain. After in vitro myotube formation, engineered tissue constructs were co-cultured for 6 days with viable embryonic heart slices. With the use of sharp electrodes, electrical coupling between engineered tissue constructs and embryonic heart slices was assessed in the presence or absence of pharmacologic agents.ResultsThe isolation and expansion procedure for skeletal myoblasts resulted in high yields of homogeneously desmin-positive (97.1% ± 0.1%) cells. Mechanical strain was exerted on myotubes within engineered tissue constructs during gelation of the matrix, generating preconditioned engineered tissue constructs. Electrical coupling between preconditioned engineered tissue constructs and embryonic heart slices was observed; however, no coupling was apparent when engineered tissue constructs were not subjected to mechanical strain. Coupling of cells from engineered tissue constructs to cells in embryonic heart slices showed slower conduction velocities than myocardial cells with the embryonic heart slices (preconditioned engineered tissue constructs vs embryonic heart slices: 0.04 ± 0.02 ms vs 0.10 ± 0.05 ms, P = .011), lower maximum stimulation frequencies (preconditioned engineered tissue constructs vs embryonic heart slices: 4.82 ± 1.42 Hz vs 10.58 ± 1.56 Hz; P = .0009), and higher sensitivities to the gap junction inhibitor (preconditioned engineered tissue constructs vs embryonic heart slices: 0.22 ± 0.07 mmol/L vs 0.93 ± 0.15 mmol/L; P = .0004).ConclusionsWe have generated skeletal myoblast-based transplantable grafts that electrically couple to myocardium.Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

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