Optogenetic Modulation of Neural Progenitor Cells Improves Neuroregenerative Potential

Abstract

Neural progenitor cell (NPC) transplantation possesses enormous potential for the treatment of disorders and injuries of the central nervous system, including the replacement of lost cells or the repair of host neural circuity after spinal cord injury (SCI). Importantly, cell-based therapies in this context still require improvements such as increased cell survival and host circuit integration, and we propose the implementation of optogenetics as a solution. Blue-light stimulation of NPCs engineered to ectopically express the excitatory light-sensitive protein channelrhodopsin-2 (ChR2-NPCs) prompted an influx of cations and a subsequent increase in proliferation and differentiation into oligodendrocytes and neurons and the polarization of astrocytes from a pro-inflammatory phenotype to a pro-regenerative/anti-inflammatory phenotype. Moreover, neurons derived from blue-light-stimulated ChR2-NPCs exhibited both increased branching and axon length and improved axon growth in the presence of axonal inhibitory drugs such as lysophosphatidic acid or chondroitin sulfate proteoglycan. Our results highlight the enormous potential of optogenetically stimulated NPCs as a means to increase neuroregeneration and improve cell therapy outcomes for enhancing better engraftments and cell identity upon transplantation in conditions such as SCI.