Directing phenotype of vascular smooth muscle cells using electrically stimulated conducting polymer

• Published in: Biomaterials Vol. 29; no. 34; pp. 4510 - 4520
• Main Authors: Rowlands, Andrew S., Cooper-White, Justin J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.12.2008
• Subjects: Actins - metabolism; Adsorption; Advanced Basic Science; Animals; Biocompatible Materials - pharmacology; Calcium - pharmacology; Cell activation; Cell Line; Cell Proliferation; Cells, Cultured; Dentistry; Electric Stimulation; Electrical stimulation; Electroactive polymer; Gene Expression Regulation - drug effects; Muscle, Smooth, Vascular - cytology; Muscle, Smooth, Vascular - drug effects; Myosin Heavy Chains - metabolism; Nifedipine - pharmacology; Phenotype; Polymers - chemistry; Polymers - pharmacology; Pyrroles - chemistry; Pyrroles - pharmacology; Rabbits; Rats; Smooth muscle cell; Spectrum Analysis; Smooth muscle cell; Cell proliferation; Electrical stimulation; Cell activation; Electroactive polymer
• ISSN: 0142-9612; 1878-5905; 1878-5905
• DOI: 10.1016/j.biomaterials.2008.07.052

Vascular smooth muscle cells (VSMCs) isolated from rabbit aorta and immortalised A7r5 cells were cultured on conducting polypyrrole (PPy) substrates and were subjected to a 50 μA sinusoidal electrical stimulation at 0.05, 5 and 500 Hz. These substrates were doped with hyaluronic acid and coated with collagen IV followed by Matrigel ® in order to mimic the basement membrane and encourage cell attachment. Increased proliferation and expression of smooth muscle phenotype markers (smooth muscle α-actin and smooth muscle myosin heavy chain) were observed in cultures stimulated at 5 and 500 Hz. This increased proliferation and expression of contractile proteins were found to be significantly decreased when L-type voltage-gated calcium channels (VGCC) were blocked with the drug nifedipine. To the best of our knowledge, this is the first work that demonstrates that VSMCs cultured on a conducting polymer substrate and subject to electrical stimulation not only exhibit enhanced proliferation but can be simultaneously encouraged to increase contractile protein expression. This behaviour is somewhat contrary to the classical definition of smooth muscle contractile and synthetic phenotypes that, in general, requires a modulation in phenotype as a prerequisite for smooth muscle proliferation. This interesting result highlights both the inherent plasticity of vascular smooth muscle cells and the potential of electrical stimulation via conducting polymer substrates to manipulate their behaviour.