Gaetani Roberto, Ledda Mario, Barile Lucio, Chimenti Isotta, De Carlo Flavia, Forte Elvira, Ionta Vittoria, Giuliani Livio, D'Emilia Enrico, Frati Giacomo, Miraldi Fabio, Pozzi Deleana, Messina Elisa, Grimaldi Settimio, Giacomello Alessandro, Lisi Antonella
Department of Experimental Medicine, Pasteur Institute, Cenci Bolognetti Foundation, Sapienza University of Rome, viale Regina Elena 324, 00161 Rome, Italy.
Cardiovasc Res. 2009 Jun 1;82(3):411-20. doi: 10.1093/cvr/cvp067. Epub 2009 Feb 19.
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.
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.
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.
以最小程度的操作调控心脏干细胞(CSC)分化是心力衰竭细胞治疗临床应用的主要目标之一。如前所述,从人心肌活检标本中获取并培养成心球(CSps)和心球衍生细胞(CDCs)的CSCs能够植入梗死心肌并使其部分再生。在本文中,我们评估了以下假设:将CSps和CDCs暴露于调谐至Ca2+离子回旋共振能量(Ca2+-ICR)的极低频电磁场(ELF-EMFs)下,可能会促使它们向心脏特异性表型分化。
在人CSps和CDCs暴露于Ca2+-ICR 5天后,在转录、翻译和表型水平均证实心脏标志物的表达显著增加。通过对Ca2+荧光探针进行分区分析观察并确认了细胞内储存库之间的Ca2+动员。
这些结果表明,调谐至Ca2+-ICR的ELF-EMFs可用于驱动成体心脏祖细胞的心脏特异性分化,而无需对用于治疗目的的细胞进行任何药理学或基因操作。