Cardiogenesis and Reversal of Stem Cell Aging by Asymmetrically Conveyed Electromagnetic Fields

Aims: Cardiogenesis, the first human morphogenetic event, is an extremely low-yield process, being severely hampered by stem cell senescence in vitro. We investigated whether exposure of human adipose-derived mesenchymal stem cells (ADhMSCs) to asymmetrically-conveyed electromagnetic fields (ACEMF) may enhance commitment to cardiovascular lineage and reverse stem cell aging.
Methods: ADhMSCs were exposed to ACEMF with a Radio-Electric-Asymmetric-Conveyer (REAC). ADhMSCs were assessed at gene and protein expression levels by real-time RT-PCR and Western blot, respectively. Confocal microscopy was used to investigate stem cell differentiation. Telomere length and telomerase activity were monitored by Telo-TAGGG telomere-length assay and TRAPEZE-RT, respectively.
Results: ACEMF primed high-throughput ADhMSC commitment towards cardiogenic and endothelial fates. REAC-mediated ACEMF also reversed senescence in ADhMSCs that had been subjected to prolonged culture up to 30 passages. This effect was mediated by re-expression of TERT, encoding the catalytic core of telomerase, leading to increased telomerase activity and telomere length. The antisenescence effect was also executed through a telomerase-independent pathway resulting from increased Bmi-1 and stemness gene transcription. The REAC action was significantly counteracted by 4-methylumbelliferone (4-MU), a potent repressor of type-2 hyaluronan (HA) synthase, indicating an essential role for the intracellular patterning of this glycosaminoglycan.
Conclusions: ACEMF can remarkably modulate stem cell cardiogenesis and senescence. HA plays a fundamental role in cell polarity and hydrodynamic processes, controlling stem cell potency and aging. Our findings indicate that endogenous HA and HA-binding proteins in the presence of REAC-mediated ACEMF may create an interesting network for the modulation of cell polarity and intracellular environment.
Key Words: Stem Cells; Cardiogenesis; Senescence; Asymmetrically Conveyed Electromagnetic Fields; Cell Polarity