Preconditioning of Skeletal Myoblast based Engineered Tissue Constructs Enables Functional Coupling to Myocardium in vivo

Philipp Treskes, Klaus Neef, Sureshkumar Perumal Srinivasan, Marcel Halbach, Christof Stamm, Douglas Cowan, Maximilian Scherner, Navid Madershahian, Thorsten Wittwer, Jurgen Hescheler, Thorsten Wahlers, Yeong-hoon Choi

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

Objective
Skeletal myoblasts fuse to form functional syncytical myotubes as an integral part of the skeletal muscle. During this differentiation process expression of proteins for mechanical and electrical integration is seized, which represents a major hindrance towards the application of skeletal myoblasts in cardiac regenerative cell therapy, as global heart function is dependent on intercellular communication.

Methods
We epicardially transplanted mechanically preconditioned engineered tissue constructs, containing neonatal mouse skeletal myoblasts. Y-chromosomal specific PCR was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histological and electrophysiological analyses were carried out one week after transplantation.

Results
Cells within the grafted construct expressed connexin 43 at the interface to the host myocardium, indicating electrical coupling, confirmed by sharp electrode recordings. Analyses on maximum stimulation frequency (5.65 ± 0.37 Hz), conduction velocity (0.087 ± 0.011 m/s) and sensitivity for pharmacological conduction block (0.736 ± 0.080 mM 1-heptanol) revealed effective electrophysiological coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency: 11.616 ± 0.238 Hz, p < 0.001; conduction velocity: 0.300 ± 0.057 m/s; p < 0.01; conduction block: 1.983 ± 0.077 mM 1-heptanol; p < 0.001).

Conclusions
While untreated skeletal myoblasts cannot couple to cardiomyocytes, we confirm that mechanical preconditioning enables transplanted skeletal myoblasts to functionally interact with cardiomyocytes in vivo and, thus, reinvigorate the concept of skeletal myoblast based cardiac cell therapy.
Original languageEnglish
JournalThe Journal of Thoracic and Cardiovascular Surgery
DOIs
Publication statusPublished - 1 Sept 2014

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