Engineered CCR2 positive macrophages coordinate immunoregulation with neural regeneration and matrix remodeling after spinal cord injury

Rationale: Spinal cord injury (SCI) triggers a complex secondary injury process characterized by inflammation, neuronal loss, extracellular matrix (ECM) disruption, and limited endogenous repair. Although cell-based therapies hold potential for SCI treatment, their efficacy is often constrained by poor lesion targeting, inadequate persistence after delivery, and limited temporal control over therapeutic factor release. Methods: , using a mouse SCI model, we evaluated lesion-site accumulation, inflammatory regulation, tissue repair, electrophysiological recovery, transcriptomic alterations, and behavioral outcomes. Results: , they attenuated inflammation, improved the local repair microenvironment, and promoted axonal regeneration, remyelination, and ECM remodeling, accompanied by partial recovery of electrophysiological and motor function after SCI. RNA-seq analysis further supported broad changes in pathways related to immune regulation, neural repair, myelination, and matrix remodeling. Conclusions: CCR2-enriched macrophages engineered with reparative mRNAs may represent a promising treatment strategy for SCI. By linking CCR2-associated lesion accumulation with multimodal reparative activity, this cell-based platform provides a potential approach for coordinated microenvironmental regulation and tissue repair.