期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 115, 期 24, 页码 E5595-E5604出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1804735115
关键词
nonhuman primate; spinal cord injury repair; chitosan; NT3; CST regeneration
资金
- National Natural Science Foundation of China [31730030, 31650001, 31670988, 31771053, 31320103903, 31620103904, 81330030, 81650110524, 31730039]
- Ministry of Science and Technology of China [2017YFC1104001, 2017YFC1104002, 2016YFA0100801, 2015CB351701]
- Beijing Science and Technology Program [Z171100002217066, Z181100001818007]
- Beijing Natural Science Foundation Program [KZ201810025030]
- Chinese Academy of Sciences [ZDYZ2015-2]
- National Institutes of Health [NIH5R21NS095184-02]
- RNAseq on Single Cell and Beyond Core in the Developmental Disabilities Research Center at the University of California, Los Angeles [NIH5U54HD087101-02]
Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.
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