An NT-3-releasing bioscaffold supports the formation of TrkC-modified neural stem cell-derived neural network tissue with efficacy in repairing spinal cord injury  

作　　者：Ge Li Bao Zhang Jia-hui Sun Li-yang Shi Meng-yao Huang Li-jun Huang Zi-jing Lin Qiong-yu Lin Bi-qin Lai Yuan-huan Ma Bin Jiang Ying Ding Hong-bo Zhang Miao-xin Li Ping Zhu Ya-qiong Wang Xiang Zeng Yuan-shan Zeng 

机构地区：[1]Key Laboratory for Stem Cells and Tissue Engineering,Ministry of Education,Sun Yat-sen University,Guangzhou,510080,China [2]Guangdong Cardiovascular Institute,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou,Guangdong,510100,China [3]Department of Histology and Embryology,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China [4]Institute of Spinal Cord Injury,Sun Yat-sen University,Guangzhou,510120,China [5]State Key Laboratory of Chemo/Biosensing and Chemometrics,College of Biology,Hunan University,Changsha,410082,China [6]Co-innovation Center of Neuroregeneration,Nantong University,Nantong,226001,China [7]Guangdong Provincial Key Laboratory of Brain Function and Disease,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China [8]Laboratory of Precision Medical Genomics,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China [9]Department of Electron Microscope,Zhongshan School of Medicine,Sun Yat-sen University,Guangzhou,510080,China

出　　处：《Bioactive Materials》2021年第11期3766-3781,共16页生物活性材料（英文）

基　　金：the Chinese National Natural Science Foundation of China(81891003);the National Key R&D Program of China(2017YFA0104700)and the 111 Project for Academic Exchange Program(B13037)to Y.S.Zeng;the Foundation of Guangdong Province(2017B020210012)to Y.S.Zeng and X.Zeng;the Co-innovation Foundation of Guangzhou City(201704020221)to Y.S.Zeng,X.Zeng,and G.Li;the Start-up Foundation of Guangdong Province(Grant No.2018A030310113)to G.Li.

摘　　要：The mechanism underlying neurogenesis during embryonic spinal cord development involves a specific ligand/receptor interaction,which may be help guide neuroengineering to boost stem cell-based neural regeneration for the structural and functional repair of spinal cord injury.Herein,we hypothesized that supplying spinal cord defects with an exogenous neural network in the NT-3/fibroin-coated gelatin sponge(NF-GS)scaffold might improve tissue repair efficacy.To test this,we engineered tropomyosin receptor kinase C(TrkC)-modified neural stem cell(NSC)-derived neural network tissue with robust viability within an NF-GS scaffold.When NSCs were genetically modified to overexpress TrkC,the NT-3 receptor,a functional neuronal population dominated the neural network tissue.The pro-regenerative niche allowed the long-term survival and phenotypic maintenance of the donor neural network tissue for up to 8 weeks in the injured spinal cord.Additionally,host nerve fibers regenerated into the graft,making synaptic connections with the donor neurons.Accordingly,motor function recovery was significantly improved in rats with spinal cord injury(SCI)that received TrkC-modified NSC-derived neural network tissue transplantation.Together,the results suggested that transplantation of the neural network tissue formed in the 3D bioactive scaffold may represent a valuable approach to study and develop therapies for SCI.

关 键 词：NEUROTROPHIN-3 Tropomyosin kinase receptor C Self-organization Neural network tissue Spinal cord injury 

分 类 号：R318[医药卫生—生物医学工程] R68[医药卫生—基础医学]