Single-cell and Spatial Omics Reveal Spinal Cord Injury Microenvironmental Heterogeneity Relevant to Neural Interfaces and Spinal Neuromodulation.

Objective

Spinal cord injury (SCI) interrupts brain-spinal communication and causes persistent motor, sensory, and autonomic deficits.

Materials And Methods

We summarize the current clinical and translational evidence on brain-computer interface (BCI)/epidural electrical stimulation (EES)/brain-spinal interface (BSI) for locomotor recovery after traumatic SCI and outline the major patterns of microenvironmental heterogeneity revealed by single-cell and spatial omics. We then link these patterns to clinically relevant axes-acute vs subacute versus chronic phases, complete vs incomplete injury, and peri-lesional vs scar-dominated regions-and discuss how they may influence circuit excitability, plasticity, and responsiveness to neuromodulation.

Results

BCIs/EESs/BSIs have enabled standing, stepping, or walking-related functions, but clinical outcomes remain highly variable. Emerging single-cell and spatial omics studies indicate that the injured spinal cord is not a uniform lesion but consists of distinct microenvironments that differ across species, anatomical regions, cell states, and stages after injury. We further propose a staged, microenvironment-aware framework linking injury stage, tissue state, and neuromodulation response through testable hypotheses. Representative clinical scenarios are presented as conceptual models rather than as prescriptive algorithms.

Conclusions

Although these relationships remain hypothesis-generating, integrating neuromodulation with omics-based profiling may provide a foundation for developing more biologically informed and individually adapted strategies for SCI rehabilitation.