NT3-chitosan Enables De Novo Regeneration and Functional Recovery in Monkeys After Spinal Cord Injury

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2018 May 31

PMID 29844162

Citations 74

Authors

Jia-Sheng Rao

Can Zhao

Aifeng Zhang

Hongmei Duan

Peng Hao

Rui-Han Wei

Junkui Shang

Wen Zhao

Zuxiang Liu

Juehua Yu

Kevin S Fan

Zhaolong Tian

Qihua He

Wei Song

Zhaoyang Yang

Yi Eve Sun

Xiaoguang Li

Affiliations

Soon will be listed here.

Abstract

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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