Intravenous Infusion of Mesenchymal Stem Cells Enhances Long-Tract Reorganization That Circumvents the Lesion in a Rat Staggered Hemisection Spinal Cord Injury Model

Background/Objectives: Non-contiguous dual spinal cord injuries are associated with poor neurological outcomes, probably due to reduced spared-tract bridges for compensatory reorganization. Intravenous (IV) infusion of mesenchymal stem cells (MSCs) promotes recovery after SCI. However, how MSCs influence long-tract reorganization across multiple lesions remains unclear. We characterized MSC-induced long-tract plasticity at two separate lesion levels using ex vivo diffusion tensor imaging (DTI) in a rat staggered hemisection model. Methods: Adult rats underwent staggered lateral hemisection at right T7 and left T12 and received IV MSCs (1 × 106) or vehicle on day 1; locomotor recovery was assessed over 4 weeks (using Basso–Beattie–Bresnahan (BBB) scale) and ex vivo DTI tractography was performed at 4 weeks (7.0 T). Results: MSC-treated rats showed significantly greater locomotor recovery than vehicle-treated rats (BBB at day 28:12.2 ± 0.6 vs. 5.4 ± 0.7, p < 0.001). MSC infusion increased total, preserved, and redirected tract counts at both lesion levels; at T7, redirected tracts entered the non-injured lateral funiculus, forming detour pathways bypassing the lesion, whereas at T12, redirected tracts from the injured-side dorsal funiculus crossed the midline into the contralateral dorsal funiculus. Conclusions: Intravenous infusion of MSCs improved locomotor outcome and altered the level-specific patterns of long tracts reconstructed from DTI data. Ex vivo DTI provides an overview of these structural changes.