Intermittent electrical stimuli for guidance of human mesenchymal stem cell lineage commitment towards neural-like cells on electroconductive substrates.
In the context of the role of multiple physical factors in dictating stem cell fate, the present paper demonstrates the effectiveness of the intermittently delivered external electric field stimulation towards switching the stem cell fate to specific lineage, when cultured in the absence of biochemical growth factors. In particular, our findings present the ability of human mesenchymal stem cells (hMSCs) to respond to the electric stimuli by adopting extended neural-like morphology on conducting polymeric substrates. Polyaniline (PANI) is selected as the model system to demonstrate this effect, as the electrical conductivity of the polymeric substrates can be systematically tailored over a broad range (10(-9) to 10 S/cm) from highly insulating to conducting by doping with varying concentrations (10(-5) to 1 m) of HCl. On the basis of the culture protocol involving the systematic delivery of intermittent electric field (dc) stimulation, the parametric window of substrate conductivity and electric field strength was established to promote significant morphological extensions, with minimal cellular damage. A time dependent morphological change in hMSCs with significant filopodial elongation was observed after 7 days of electrically stimulated culture. Concomitant with morphological changes, a commensurate increase in the expression of neural lineage commitment markers such as nestin and βIII tubulin was recorded from hMSCs grown on highly conducting substrates, as revealed from the mRNA expression analysis using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) as well as by immune-fluorescence imaging. Therefore, the present work establishes the key role of intermittent and systematic delivery of electric stimuli as guidance cues in promoting neural-like differentiation of hMSCs, when grown on electroconductive substrates.
['Thrivikraman|Greeshma|G|', 'Madras|Giridhar|G|', 'Basu|Bikramjit|B|']
D000814:Aniline Compounds D017209:Apoptosis D015415:Biomarkers D002452:Cell Count D019070:Cell Lineage D049109:Cell Proliferation D048430:Cell Shape D002470:Cell Survival D004553:Electric Conductivity D004558:Electric Stimulation D005434:Flow Cytometry D005786:Gene Expression Regulation D006801:Humans D007150:Immunohistochemistry D059630:Mesenchymal Stem Cells D008954:Models, Biological D064231:Nestin D009474:Neurons D018384:Oxidative Stress D010641:Phenotype D056951:Photoelectron Spectroscopy D013816:Thermodynamics
Mesenchymal stem cells Electric field Polyaniline Substrate conductivity Neural-like differentiation