Simultaneous monitoring of electrophysiology and neurotransmitter release in biohybrid neural implants for Parkinson's Disease

Parkinson’s disease (PD) is characterized by the degeneration of mesencephalic dopaminergic (mesDA) neurons which leads to bradykinesia, tremor, and muscle rigidity. As such, the replacement of mesDA neurons holds great promise in treating PD. Cell therapies can overcome the unpredictability of dosing as well as off-target effects of oral medications which can lead to other psychiatric problems. However, the survival of transplanted cells is poor, and adjunct interventions are thus needed to improve graft survival and normal development of transplanted cells. We propose a biohybrid approach to cell replacement therapy by integrating thin-film electronic implants with transplanted human embryonic stem cell-derived dopaminergic neurons. By interfacing transparent PEDOT:PSS microelectrodes with mesDA neurons, we can simultaneously monitor electrophysiology and dopamine release in real-time in vitro. Future studies in the 6-OHDA model of PD in rats will allow further insights into the maturation of transplanted mesDA neurons in vivo as the activity of transplanted cells is currently not well understood. Furthermore, electrical stimulation of neural stem cells has been shown to enhance cell proliferation, survival, and neurite outgrowth. By optimizing stimulation protocols, we can potentially decrease time to functional maturity of grafts, which otherwise only reach maturity starting from 6 weeks to 6 months after transplantation. Bioelectric cues have significant advantages over biochemical stimuli, which degrade or are exhausted over time and must be continuously supplied. Our proposed biohybrid neural implants can directly monitor transplanted cells and actively control treatment, thus offering the potential to greatly enhance the efficacy of advanced stem cell therapies.