Universität zu Köln

Treskes, Philipp, Neef, Klaus, Srinivasan, Sureshkumar Perumal, Halbach, Marcel, Stamm, Christof, Cowan, Douglas, Scherner, Maximilian, Madershahian, Navid, Wittwer, Thorsten, Hescheler, Juergen, Wahlers, Thorsten and Choi, Yeong-Hoon (2015). Preconditioning of skeletal myoblast-based engineered tissue constructs enables functional coupling to myocardium in vivo. J. Thorac. Cardiovasc. Surg., 149 (1). S. 348 - 357. NEW YORK: MOSBY-ELSEVIER. ISSN 1097-685X

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Abstract

Objective: Skeletal myoblasts fuse to form functional syncytial myotubes as an integral part of the skeletal muscle. During this differentiation process, expression of proteins for mechanical and electrical integration is seized, which is a major drawback for the application of skeletal myoblasts in cardiac regenerative cell therapy, because global heart function depends on intercellular communication. Methods: Mechanically preconditioned engineered tissue constructs containing neonatal mouse skeletal myoblasts were transplanted epicardially. A Y-chromosomal specific polymerase chain reaction (PCR) was undertaken up to 10 weeks after transplantation to confirm the presence of grafted cells. Histologic and electrophysiologic analyses were carried out 1 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 of the maximum stimulation frequency (5.65 +/- 0.37 Hz), conduction velocity (0.087 +/- 0.011 m/s) and sensitivity for pharmacologic conduction block (0.736 +/- 0.080 mM 1-heptanol) revealed effective electrophysiologic coupling between graft and host cells, although significantly less robust than in native myocardial tissue (maximum stimulation frequency, 11.616 +/- 0.238 Hz, P < .001; conduction velocity, 0.300 +/- 0.057 m/s, P < .01; conduction block, 1.983 +/- 0.077 mM 1-heptanol, P < .001). Conclusions: Although 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Treskes, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Neef, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Srinivasan, Sureshkumar Perumal UNSPECIFIED UNSPECIFIED UNSPECIFIED Halbach, Marcel UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamm, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Cowan, Douglas UNSPECIFIED UNSPECIFIED UNSPECIFIED Scherner, Maximilian UNSPECIFIED UNSPECIFIED UNSPECIFIED Madershahian, Navid UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittwer, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Yeong-Hoon UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-417113
DOI:	10.1016/j.jtcvs.2014.09.034
Journal or Publication Title:	J. Thorac. Cardiovasc. Surg.
Volume:	149
Number:	1
Page Range:	S. 348 - 357
Date:	2015
Publisher:	MOSBY-ELSEVIER
Place of Publication:	NEW YORK
ISSN:	1097-685X
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language CELL TRANSPLANTATION; EXPRESSION; OVEREXPRESSION; CONNEXIN-43; INTEGRATION; ENGRAFTMENT; CONDUCTION; MODEL Multiple languages Cardiac & Cardiovascular Systems; Respiratory System; Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/41711