A Chitosan Scaffold Infused With Neurotrophin-3 And Human Umbilical Cord Mesenchymal Stem Cells Suppresses Inflammation And Promotes Functional Recovery After Spinal Cord Injury In Mice

INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL MEDICINE(2017)

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摘要
Despite the severe consequences of spinal cord injuries (SCI), effective treatments are lacking. In this study, the ability of chitosan/neurotrophin-3 (NT3) scaffolds seeded with human umbilical cord mesenchymal stem cells (hUC-MSCs) to treat SCI was investigated. The structure of chitosan/NT3 scaffolds and their effects on proliferation were detected by scanning electron microscopy and MTT assays. The scaffold was implanted into the injured site of SCI mouse models to evaluate its treatment ability. After 8 weeks, locomotor functional recovery was evaluated based on Basso mouse scale (BMS) assessment scores and a CatWalk automated quantitative gait analysis. The density and shape of nissl's body were measured by Nissl staining. The expression of ionized calcium-binding adapter molecules 1 (Iba1) and inflammatory cytokine levels were analyzed. Isolated hUC-MSCs exhibited abundant expression of mesenchymal stem cell surface markers (CD73, CD90, and CD105). The chitosan/NT3 scaffold had a dense shell and a porous core, which did not affect hUC-MSC proliferation. The chitosan/NT-3+hUC-MSCs treatment significantly improved indicators of locomotion ability, and promoted neuron regeneration. The chitosan/NT3+hUCMSCs treatment inhibited Iba-1 expression, suppressed microglia activation, reduced MIP-1 beta, IL-6, IL-17, MCP-1, and MIP-1 alpha levels, and increased IL-10 levels. The ability of chitosan/NT3+hUC-MSCs to promote SCI recovery was stronger than those of chitosan/NT3 and chitosan+hUC-MSCs. Chitosan/NT3+hUC-MSCs treatment could reduce inflammation, silence microglia, promote neuron regeneration, and enhance the recovery of neurological function after SCI. Thus, these scaffolds open new and promising avenues for SCI treatment.
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关键词
spinal cord injury, chitosan, neurotrophin-3, human umbilical cord mesenchymal stem cells, inflammation
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