Long-Term Selective Stimulation of Transplanted Neural Stem/Progenitor Cells for Spinal Cord Injury Improves Locomotor Function

In cell transplantation therapy for spinal cord injury (SCI), grafted  human induced pluripotent stem  cell-derived  neural stem/progenitor cells  (hiPSC-NS/PCs) mainly differentiate into neurons, forming synapses in a similar process to neural development. In the developing nervous system, the activities of immature neurons play important roles in constructing and maintaining new synapses. Thus, we investigated how the enhanced activity of transplanted hiPSC-NS/PCs affects themselves and the host tissue.  We found that chemogenetic stimulation of hiPSC-derived neural cells enhanced cell activity and neuron-to-neuron interactions in vitro. In a rodent model of SCI, consecutive and selective chemogenetic stimulation of transplanted hiPSC-NS/PCs also enhanced the expression of synapse-related genes and proteins in surrounding host tissues and prevented atrophy of the injured spinal cord, resulting in improved locomotor functions. These findings suggest a strategy to enhance activity within the graft to improve the efficacy of cell transplantation therapy for SCI.