Electrical Stimulation Enhanced Mesenchymal Stem Cell Gene Expression for Orthopaedic Tissue Repair

Non-union fractures and large-size defects in bone affect the quality of life of millions of patients around the world. However, the lack of suitable donor tissue limits the scope of traditional bone graft treatments. Tissue engineered implants have the potential to overcome these problems, whilst electrical stimulation has been shown to enhance the proliferation, gene expression and ECM deposition of bone cells in vitro. Applying the same modality to Mesenchymal Stem Cells could provide an invaluable tool for the treatment of non-unions and bone tissue engineering. Primary human Mesenchymal Stem Cells cultured in custom-made bioreactors were stimulated with voltage pulses of varying regimes. Cell numbers/viability were measured using Alamar Blue staining, while viability, morphology and alignment were assessed using Live/Dead staining. The expression of 11 markers of differentiation and Vascular Endothelial Growth Factor was assayed in growth and osteogenic medium. Gene expression was unaffected in the growth medium, with the exception of a significant decrease of CNN1 levels whilst in the osteogenic medium, the stimulation significantly altered ALPL, ACAN, CNN1 and GFAP expressions. Proliferation was lowered in the majority of electrical regimes applied. This study demonstrates that direct electrical stimulation can influence both the differentiation and proliferation of human Mesenchymal Stem Cells.