Enhanced Proliferation of Endothelial Progenitor Cells Post-Ultrasonic Microbubble Transfection Is Plasmid DNA Size Dependent and Contributed by Interleukin-6 Generation.

We investigated whether ultrasonic microbubble transfection (UMT) would enhance the transfection of large-sized luciferase plasmids (5.6, 9.2 and 33 kb) and biological impacts. Porcine venous blood endothelial progenitor cells (EPCs) were cultured in a medium containing plasmid DNA (pDNA) of different sizes followed by UMT and functional assays. Real-time polymerase chain reaction was conducted to investigate the effects of transfection of pDNA on multiple molecules central to endothelial function. The results indicated enhanced luciferase expression after UMT but the enhancement declined with increase in the size of the plasmid. UMT of pDNAs sized 5.6 and 9.2 kb into EPCs led to significant enhancement of proliferation. The interleukin-6 (IL-6) secreted from UMT of EPCs also increased in the 5.6- and 9.2-kb pDNA groups. Treatment of the transfected EPCs with anti-IL-6 antibody neutralized the proliferation. In conclusion, UMT of pDNAs sized 5.6 and 9.2 kb into EPCs increased the secretion of IL-6, which in turn enhanced cell proliferation.