Human spinal interneurons repair the injured spinal cord through synaptic integration

Endogenous V2a spinal interneurons (SpINs) have been implicated as a key component in recovery post-SCI, but the integration of these cells with injured host networks after transplantation has been unexplored. We show that transplanted human stem cell-derived V2a-enriched SpINs functionally integrate with the host rat injured spinal cord after cervical SCI.

Neural tracing and optogenetic stimulation of transplanted cells and host supraspinal pathways reveal functional host-transplant-host connectivity, reflecting a functional neuronal relay. Single-cell transcriptomic analyses pre- and post-transplantation confirmed maturation of transplanted SpINs and glial progenitors involved in spinal cord repair, and revealed genes that were specific to V2a SpINs synapsing with the host phrenic motor network.