Abstract
Electrical stimulation is increasingly being used to modulate human cell behaviour for biotechnological research and therapeutics. Electrically conductive polymers (CPs) such as polypyrrole (PPy) are amenable to in vitro and in vivo cell stimulation, being easy to synthesise with different counter ions (dopants) to augment biocompatibility and cell-effects. Extending our earlier work, which showed that CP-mediated electrical stimulation promotes human neural stem cell differentiation, here we report using electroactive PPy containing the anionic dopant dodecylbenzenesulfonate (DBS) to modulate the fate determination of human induced pluripotent stem cells (iPSCs). Remarkably, the stimulation without conventional chemical inducers resulted in the iPSCs differentiating to cells of the three germ lineages—endoderm, ectoderm, and mesoderm. The unstimulated iPSC controls remained undifferentiated. Phenotypic characterisation further showed a robust induction to neuronal fate with electrical stimulation, again without customary chemical inducers. Our findings add to the growing body of evidence supporting the use of electrical stimulation to augment stem cell differentiation, more specifically, pluripotent stem cell differentiation, and especially neuronal induction. Moreover, we have shown the versatility of electroactive PPy as a cell-compatible platform for advanced stem cell research and translation, including identifying novel mechanisms of fate regulation, tissue development, electroceuticals, and regenerative medicine.
Highlights
Living cells and tissues produce and respond to bioelectric potentials, which may vary depending on their developmental and pathophysiological state [1]
Our findings provide proof-of-concept for the use of electrical stimulation to standardise stem cell differentiation and add to the growing body of evidence for the in vitro and in vivo versatility of electroactive conductive polymers (CPs) such as PPy as stable and cytocompatible platforms for advanced stem cell research and translation
We describe the use of electrical stimulation for differentiating human induced pluripotent stem cells (iPSCs) and expound the versatility of electroactive PPy:DBS
Summary
Living cells and tissues produce and respond to bioelectric potentials, which may vary depending on their developmental and pathophysiological state [1]. Notwithstanding earlier recognition of the significance of bioelectricity and therapeutic stimulation, researchers have only recently begun to explore the potential of electric stimulus in vitro. We and others have investigated electrical stimulation for modulating cell behaviour initially under conventional two-dimensional (2D)/planar culture and more recently for three-dimensional (3D) tissue engineering [5,6,7,8]. The stimulation of NSCs using electroactive PPy:DBS film or ESCs by electroporation of embryoid bodies (EBs) with or without conventional chemically-based inducers showed robust neuronal but less glial cell induction. Novel 3D electrical stimulation of human NSCs within a conductive bio-gel using printed polymer poly(3,4-ethylenedioxythiophene)-polystyrenesulfonate (PEDOT:PSS) pillar microelectrodes enabled the development and maturation of 3D human neural tissues with enhanced neuronal cell function and increased response to drug-induced disinhibition [5]
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