Universität zu Köln

Neef, Klaus, Choi, Yeong-Hoon, Srinivasan, Sureshkumar Perumal, Treskes, Philipp, Cowan, Douglas B., Stamm, Christof, Rubach, Martin, Adelmann, Roland, Wittwer, Thorsten and Wahlers, Thorsten (2012). Mechanical preconditioning enables electrophysiologic coupling of skeletal myoblast cells to myocardium. J. Thorac. Cardiovasc. Surg., 144 (5). S. 1176 - 1186. NEW YORK: MOSBY-ELSEVIER. ISSN 0022-5223

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Abstract

Objective: The 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. Methods: Murine 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. Results: The 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). Conclusions: We have generated skeletal myoblast-based transplantable grafts that electrically couple to myocardium. (J Thorac Cardiovasc Surg 2012;144:1176-84)

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Neef, Klaus UNSPECIFIED UNSPECIFIED UNSPECIFIED Choi, Yeong-Hoon UNSPECIFIED UNSPECIFIED UNSPECIFIED Srinivasan, Sureshkumar Perumal UNSPECIFIED UNSPECIFIED UNSPECIFIED Treskes, Philipp UNSPECIFIED UNSPECIFIED UNSPECIFIED Cowan, Douglas B. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stamm, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Rubach, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Adelmann, Roland UNSPECIFIED UNSPECIFIED UNSPECIFIED Wittwer, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Wahlers, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-480126
DOI:	10.1016/j.jtcvs.2012.07.036
Journal or Publication Title:	J. Thorac. Cardiovasc. Surg.
Volume:	144
Number:	5
Page Range:	S. 1176 - 1186
Date:	2012
Publisher:	MOSBY-ELSEVIER
Place of Publication:	NEW YORK
ISSN:	0022-5223
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language STEM-CELLS; ISCHEMIC CARDIOMYOPATHY; SATELLITE CELLS; TRANSPLANTATION; CARDIOMYOCYTES; MUSCLE; HEART; EXPRESSION; CONNEXIN43; THERAPY Multiple languages Cardiac & Cardiovascular Systems; Respiratory System; Surgery Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/48012