Electromagnetic Biology and Medicine, 27: 127–133, 2008 Copyright C Informa Healthcare USA, Inc. ISSN 1536-8378 print/1536-8386 online DOI: 10.1080/15368370802072117 Ion Cyclotron Resonance as a Tool in Regenerative Medicine ANTONELLA LISI 1 , MARIO LEDDA 1 , FLAVIA DE CARLO 1 , DELEANA POZZI 2 , ELISA MESSINA 2 , ROBERTO GAETANI 2 , ISOTTA CHIMENTI 2 , LUCIO BARILE 2 , ALESSANDRO GIACOMELLO 2 , ENRICO D’EMILIA 3 , LIVIO GIULIANI 3 , ALBERTO FOLETTI 4 , ANNAMARIA PATTI 5 , ANTONELLA VULCANO 5 , AND SETTIMIO GRIMALDI 1 1 Istituto di Neurobiologia e Medicina Molecolare, Rome, Italy 2 Dipartimento di Medicina, Sperimentale Universita` ‘‘La Sapienza,’’ Rome, Italy 3 ISPESL DIPIA, Rome, Italy 4 Bititalia, Milano, Italy 5 Dipartimento di Scienze e Sanita` Publica ‘‘G Sanarelli,’’ Universita` la Sapienza, Rome, Italy The identification of suitable stem cell cultures and differentiating conditions that are free of xenogenic growth supplements is an important step in finding the clinical applicability of cell therapy in two important fields of human medicine: heart failure and bone remodeling, growth and repair. We recently demonstrated the possibility of obtaining cardiac stem cells (CSCs) from human endomyocardial biopsy specimens. CSCs self- assemble into multi-cellular clusters known as cardiospheres (CSps) that engraft and partially regenerate infarcted myocardium. CSps and cardiosphere-derived-cells (CDCs) were exposed for five days in an incubator regulated for temperature, humidity, and CO 2 inside a solenoid system. This system was placed in a magnetically shielded room. The cells were exposed simultaneously to a static magnetic field (MF) and a parallel low- alternating frequency MF, close to the cyclotron frequency corresponding to the charge/ mass ratio of the Ca þþ ion. In this exposure condition, CSps and CDCs modulate their differentiation turning on cardiogenesis and turning off vasculogenesis. Cardiac markers such as troponin I (TnI) and myosin heavy chain (MHC) were up-regulated. Conversely, angiogenic markers such as vascular endothelial growth factor (VEGF) and kinase domain receptor (KDR) were down-regulated as evidenced by immunocytochemistry. Exposure to the 7 Hz calcium ion cyclotron resonance (ICR) frequency can modulate the cardiogenic vs. angiogenic differentiation process of ex vivo expanded CSCs. This may pave the way for novel approaches in tissue engineering and cell therapy. Address correspondence to Settimio Grimaldi, Institute of Neurobiology and Molecolar Medicine, Area Ricerca Tor Vergata CNR, Rome, Italy; E-mail: settimio.grimaldi@artov. inmm.cnr.it 127 Electromagn Biol Med Downloaded from informahealthcare.com by European oncology on 04/13/12 For personal use only.