Fetal rat neural progenitor cell transplantation after spinal cord injury improves motor recovery following optogenetic stimulation

Spinal cord injury (SCI) disrupts communication between the brain and the spinal circuits, resulting in severe motor, sensory, and autonomic dysfunctions. Transplantation of neural progenitor cells (NPCs) has been demonstrated to provide multiple benefits; however, limited graft survival and neuronal differentiation must be overcome to achieve improved results. Here, we explore the optogenetic modulation of rat spinal cord-derived NPC expressing channelrhodopsin-2 (ChR2) through adeno-associated virus serotype 9-mediated transduction, transplanted into the sub-acute stage after SCI. Daily blue-light stimulation and ChR2-dependent activation control of the modified NPC significantly enhanced locomotor skills, run speed, sustained walking coordination, and body stability in a rat SCI model. Engrafted rat NPC-ChR2 reduces astrocytic reactivity and the injured area volume, preserves a higher number of descending propriospinal neurons above the injury and a higher innervation of 5-hydroxytryptamine fibers to choline acetyltransferase-positive motoneurons below the injury, and the increased vesicular glutamate transporter expression suggests an enhanced excitatory synaptic activity. Overall, sustained activation of rat NPC post-transplantation offers a promising strategy for improved locomotor recovery following SCI.