Single-cell analysis reveals region-heterogeneous responses in rhesus monkey spinal cord with complete injury

Spinal cord injury (SCI) leads to severe sensory and motor dysfunction below the lesion. However, the cellular heterogeneity and dynamic responses in different regions below the lesion remain to be elusive. Here, we used single-cell transcriptomics to characterize the region-related cellular responses in complete thoracic SCI of rhesus monkeys from the acute to the chronic phase. We found that cells in the distal lumbar tissue were severely affected and generated a degenerative microenvironment dominated by sustained activation of phagocytic microglia, increased inhibitory interneurons, and demyelinated oligodendrocytes after SCI. Furthermore, we revealed scaffold implantation in the injury sites could improve the microenvironment of injury sites by regulating glial cells and fibroblasts, and remodel the spared lumbar tissues by decreasing the inhibitory neurons and enhancing phagocytosis and remyelination. Our findings provide comprehensive pathological insights into the spared distal tissues and proximal tissues after SCI, highlighting the importance of scaffold-based treatment strategies for targeting heterogeneous microenvironments. Different regions of the completely injured rhesus monkey spinal cord from the acute phases (7 days and 14 days) to chronic phases (30 days and 6 months) and the cellular responses with functional scaffold (LOCS + Cetuximab) implantation after 6 months were analyzed using scRNA-seq.