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Cardiovascular Research Advance Access [Accepted Manuscript] published online on February 19, 2009
Cardiovascular Research, doi:10.1093/cvr/cvp067
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2009. For permissions please email: journals.permissions@oxfordjournals.org.

Differentiation of human adult cardiac stem cells exposed to Extremely Low Frequency Electromagnetic Fields

Roberto Gaetani•,#, Mario Ledda{blacksquare},#, Lucio Barile•, Isotta Chimenti•, Flavia De Carlo{blacksquare}, Elvira Forte•, Vittoria Ionta•, Livio Giuliani{blacktriangleup}, Enrico D'Emilia{blacktriangleup}, Giacomo Frati{circ},•, Fabio Miraldi{triangleup}, Deleana Pozzi•, Elisa Messina•, Settimio Grimaldi{blacksquare}, Alessandro Giacomello•,* and Antonella Lisi{blacksquare}

• Department of Experimental Medicine, Pasteur Institute, Cenci Bolognetti Foundation, University of Rome "Sapienza", viale Regina Elena 324, 00161 Rome.
{circ} Department of Cardiac Surgery, University of Rome "Sapienza" Polo Pontino-ICOT, 04100 Latina and I.R.C.C.S. Neuromed, 86077 Pozzilli (Italy).
{blacksquare} Institute of Neurobiology and Molecular Medicine, CNR, via Fosso del Cavaliere 100, 00133 Rome (Italy).
{blacktriangleup} ISPESL-DIPIA Rome (Italy).
{triangleup} Department of Heart and Great Vessels "Attilio Reale", University of Rome "Sapienza", viale Regina Elena 324, 00161 Rome (Italy).

* Corresponding author: Alessandro Giacomello, MD, PhD, Department of Experimental Medicine, University of Rome "Sapienza", viale Regina Elena 324, 00161 Rome (Italy), Tel/fax: +39064461481. alessandro.giacomello{at}uniroma1.it.

Aims: Modulation of cardiac stem cell (CSC) differentiation with minimal manipulation is one of the main goals of clinical applicability of cell therapy for heart failure. CSCs, obtained from human myocardial bioptic specimens and grown as cardiospheres (CSps) and cardiosphere-derived cells (CDCs), can engraft and partially regenerate the infarcted myocardium, as previously described. In this paper we assessed the hypothesis that exposure of CSps and CDCs to extremely low frequency electromagnetic fields (ELF-EMFs), tuned at Ca2+ ion cyclotron energy resonance (Ca2+-ICR), may drive their differentiation towards a cardiac-specific phenotype.

Methods and results: A significant increase in the expression of cardiac markers was observed after 5 days of exposure to Ca2+-ICR in both human CSps and CDCs, as evidenced at transcriptional, translational and phenotypical levels. Ca2+ mobilization among intracellular storages was observed and confirmed by compartmentalized analysis of Ca2+ fluorescent probes.

Conclusions: These results suggest that ELF-EMFs tuned at Ca2+-ICR could be used to drive cardiac-specific differentiation in adult cardiac progenitor cells without any pharmacological or genetic manipulation of the cells that will be used for therapeutic purposes.

Time for primary review: 23 Days

# Authors contributed equally to the study.


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