Turning on stem cell cardiogenesis with extremely low frequency magnetic fields.
Modulation of stem cell differentiation is an important assignment for cellular engineering. Embryonic stem (ES) cells can differentiate into cardiomyocytes, but the efficiency is typically low. Here, we show that exposure of mouse ES cells to extremely low frequency magnetic fields triggered the expression of GATA-4 and Nkx-2.5, acting as cardiac lineage-promoting genes in different animal species, including humans. Magnetic fields also enhanced prodynorphin gene expression, and the synthesis and secretion of dynorphin B, an endorphin playing a major role in cardiogenesis. These effects occurred at the transcriptional level and ultimately ensued into a remarkable increase in the yield of ES-derived cardiomyocytes. These results demonstrate the potential use of magnetic fields for modifying the gene program of cardiac differentiation in ES cells without the aid of gene transfer technologies and may pave the way for novel approaches in tissue engineering and cell therapy.
Ventura
Carlo
C
Laboratory of Molecular Biology and Stem Cell Engineering, National Institute of Biostructures and Biosystems, University of Bologna, Bologna, Italy. cvent@libero.it
Maioli
Margherita
M
Asara
Yolande
Y
Santoni
Daniela
D
Mesirca
Pietro
P
Remondini
Daniel
D
Bersani
Ferdinando
F
D002454:Cell Differentiation / Q000502:physiology / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000235:genetics / Q000528:radiation effects; D004622:Embryo, Mammalian / Q000166:cytology* / Q000528:radiation effects; D004745:Enkephalins / Q000235:genetics / Q000528:radiation effects; D050991:GATA4 Transcription Factor; D005786:Gene Expression Regulation / Q000502:physiology / Q000528:radiation effects; D006321:Heart / Q000196:embryology* / Q000528:radiation effects*; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins / Q000235:genetics / Q000528:radiation effects; D006801:Humans; D008280:Magnetics / Q000145:classification; D009206:Myocardium / Q000166:cytology; D032383:Myocytes, Cardiac / Q000502:physiology / Q000528:radiation effects; D038081:Organogenesis / Q000502:physiology / Q000528:radiation effects; D011498:Protein Precursors / Q000235:genetics / Q000528:radiation effects; D011840:Radiation, Nonionizing; D013234:Stem Cells / Q000502:physiology* / Q000528:radiation effects*; D023822:Tissue Engineering / Q000379:methods; D014157:Transcription Factors / Q000235:genetics / Q000528:radiation effects
D004268:DNA-Binding Proteins; D004745:Enkephalins; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D000072576:Homeobox Protein Nkx-2.5; D018398:Homeodomain Proteins; C095552:NKX2-5 protein, human; D011498:Protein Precursors; D014157:Transcription Factors; C033660:preproenkephalin