The possibility that resident myocardial progenitor cells may be re-activated by transplantation of exogenous stem cells into the post-infarcted heart has been suggested as a possible mechanism to explain the heart's functional improvement after stem cell therapy. Here we studied whether differentiation of mouse neonatal immature cardiomyocytes in vitro was influenced by mouse skeletal myoblasts C2C12, wild type or engineered to secrete the cardiotropic hormone relaxin. The cultured cardiomyocytes formed spontaneously beating clusters and temporally exhibited cardiac immunophenotypical (cKit, atrial natriuretic peptide, troponin T, connexin-43, HCN4) and electrical features (inward voltage-dependent Na(+), T- and L-type Ca(2+) currents, outward and inward K(+) currents, I(f) pacemaker current). These clusters were functionally connected through nanotubular structures and undifferentiated cardiac cells in the form of flattened stripes, bridging the clusters through connexin-43-containing gap junctions. These findings suggested the existence of long distance cell-to-cell communications among the cardiomyocyte aggregates involved in the intercellular transfer of Ca(2+) signals and organelles, likely required for coordination of myocardial differentiation. Co-presence of the myoblasts greatly increased cardiomyocyte differentiation and the amount of intercellular connections. In fact, these cells formed a structural support guiding elongation of nanotubules and stripe-like cells. The secretion of relaxin by the engineered myoblasts accelerated and enhanced the cardiomyogenic potential of the co-culture. These findings underscore the possibility that grafted myoblasts and cardiotropic factors, such as relaxin, may influence regeneration of resident immature cardiac cells, thus adding a the to the mosaic of mechanisms involved in the functional benefits of cell transplantation for cardiac repair. (C) 2009 Elsevier Inc. All rights reserved.

Skeletal myoblasts overexpressing relaxin improve differentiation and communication of primary murine cardiomyocyte cell cultures / Lucia, Formigli; Fabio, Francini; Silvia, Nistri; Martina, Margheri; Giorgia, Luciani; Naro, Fabio; J. D., Silvertow; Sandra Zecchi, Orlandini; Elisabetta, Meacci; Daniele, Bani. - In: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. - ISSN 0022-2828. - 47:2(2009), pp. 335-345. [10.1016/j.yjmcc.2009.05.008]

Skeletal myoblasts overexpressing relaxin improve differentiation and communication of primary murine cardiomyocyte cell cultures

NARO, Fabio;
2009

Abstract

The possibility that resident myocardial progenitor cells may be re-activated by transplantation of exogenous stem cells into the post-infarcted heart has been suggested as a possible mechanism to explain the heart's functional improvement after stem cell therapy. Here we studied whether differentiation of mouse neonatal immature cardiomyocytes in vitro was influenced by mouse skeletal myoblasts C2C12, wild type or engineered to secrete the cardiotropic hormone relaxin. The cultured cardiomyocytes formed spontaneously beating clusters and temporally exhibited cardiac immunophenotypical (cKit, atrial natriuretic peptide, troponin T, connexin-43, HCN4) and electrical features (inward voltage-dependent Na(+), T- and L-type Ca(2+) currents, outward and inward K(+) currents, I(f) pacemaker current). These clusters were functionally connected through nanotubular structures and undifferentiated cardiac cells in the form of flattened stripes, bridging the clusters through connexin-43-containing gap junctions. These findings suggested the existence of long distance cell-to-cell communications among the cardiomyocyte aggregates involved in the intercellular transfer of Ca(2+) signals and organelles, likely required for coordination of myocardial differentiation. Co-presence of the myoblasts greatly increased cardiomyocyte differentiation and the amount of intercellular connections. In fact, these cells formed a structural support guiding elongation of nanotubules and stripe-like cells. The secretion of relaxin by the engineered myoblasts accelerated and enhanced the cardiomyogenic potential of the co-culture. These findings underscore the possibility that grafted myoblasts and cardiotropic factors, such as relaxin, may influence regeneration of resident immature cardiac cells, thus adding a the to the mosaic of mechanisms involved in the functional benefits of cell transplantation for cardiac repair. (C) 2009 Elsevier Inc. All rights reserved.
2009
c2c12 myoblasts; cardiomyocytes; gap junctions; myocardial differentiation; relaxin
01 Pubblicazione su rivista::01a Articolo in rivista
Skeletal myoblasts overexpressing relaxin improve differentiation and communication of primary murine cardiomyocyte cell cultures / Lucia, Formigli; Fabio, Francini; Silvia, Nistri; Martina, Margheri; Giorgia, Luciani; Naro, Fabio; J. D., Silvertow; Sandra Zecchi, Orlandini; Elisabetta, Meacci; Daniele, Bani. - In: JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY. - ISSN 0022-2828. - 47:2(2009), pp. 335-345. [10.1016/j.yjmcc.2009.05.008]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/123438
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