机构:[a]Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, 100083 Beijing, China[b]Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 100083 Beijing, China[c]Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, 100083 Beijing, China[d]Beijing Friendship Hospital, Capital Medical University, 100068 Beijing, China[e]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China[f]State Key Laboratory of Brain and Cognitive Science, Institute of Biophysics, Chinese Academy of Sciences, 100101 Beijing, China[g]Innovation Center of Excellence on Brain Science, Chinese Academy of Sciences, 100101 Beijing, China[h]Department of Biology, College of Life Sciences, University of Chinese Academy of Sciences, 100049 Beijing, China[i]Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China[j]Department of Computer Engineering, University of California, Santa Barbara, CA 93106[k]Department of Anesthesiology, Xuanwu Hospital Capital Medical University, 100053 Beijing, China麻醉手术科首都医科大学宣武医院[l]Centre of Medical and Health Analysis, Peking University Health Science Center, 100191 Beijing, China[m]Rehabilitation Engineering Research Institute, China Rehabilitation Research Center, 100068 Beijing, China[n]Department of Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095
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.
基金:
the National Natural Science Foundation of China (Grants 31730030, 31650001, 31670988, 31771053, 31320103903, 31620103904, 81330030, 81650110524, and 31730039),
Ministry of Science and Technology of China (Grants 2017YFC1104001, 2017YFC1104002, 2016YFA0100801, and 2015CB351701),
Beijing Science and Technology Program (Grants Z171100002217066 and Z181100001818007),
Beijing Natural Science Foundation Program (Grant KZ201810025030),
Chinese Academy of Sciences (Grant ZDYZ2015-2).
the National Institutes of Health (NIH5R21NS095184-02) and “RNAseq on Single Cell and Beyond Core”in the Developmental Disabilities Research Center (NIH5U54HD087101-02) at the University of California, Los Angeles.
第一作者机构:[a]Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, 100083 Beijing, China[b]Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 100083 Beijing, China[c]Beijing Advanced Innovation Center for Biomedical Engineering, Beihang University, 100083 Beijing, China
共同第一作者:
通讯作者:
通讯机构:[a]Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beihang University, 100083 Beijing, China[b]Beijing International Cooperation Bases for Science and Technology on Biomaterials and Neural Regeneration, Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, 100083 Beijing, China[e]Department of Neurobiology, School of Basic Medical Sciences, Capital Medical University, 100069 Beijing, China[i]Translational Stem Cell Research Center, Tongji Hospital, Tongji University School of Medicine, 200065 Shanghai, China[n]Department of Psychiatry and Biobehavioral Sciences, UCLA Medical School, Los Angeles, CA 90095
推荐引用方式(GB/T 7714):
Jia-Sheng Rao,Can Zhao,Aifeng Zhang,et al.NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury[J].PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA.2018,115(24):E5595-E5604.doi:10.1073/pnas.1804735115.
APA:
Jia-Sheng Rao,Can Zhao,Aifeng Zhang,Hongmei Duan,Peng Hao...&Xiaoguang Li.(2018).NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA,115,(24)
MLA:
Jia-Sheng Rao,et al."NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury".PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 115..24(2018):E5595-E5604