Allotransplantation of adult spinal cord tissues after complete transected spinal cord injury: long-term survival and functional recovery in canines

作     者：He Shen Shuyu Wu Xi Chen Bai Xu Dezun Ma Yannan Zhao Yan Zhuang Bing Chen Xianglin Hou Jiayin Li Yudong Cao Xianyong Fu Jun Tan Wen Yin Juan Li Li Meng Ya Shi Zhifeng Xiao Xingjun Jiang Jianwu Dai He Shen;Shuyu Wu;Xi Chen;Bai Xu;Dezun Ma;Yannan Zhao;Yan Zhuang;Bing Chen;Xianglin Hou;Jiayin Li;Yudong Cao;Xianyong Fu;Jun Tan;Wen Yin;Juan Li;Li Meng;Ya Shi;Zhifeng Xiao;Xingjun Jiang;Jianwu Dai

作者机构：Key Laboratory for Nano-Bio Interface ResearchDivision of NanobiomedicineSuzhou Institute of Nano-Tech and Nano-BionicsChinese Academy of SciencesSuzhou 215123China State Key Laboratory of Molecular Developmental BiologyInstitute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Department of NeurosurgeryXiangya HospitalCentral South UniversityChangsha 410008China Shigatse BranchXinqiao HospitalArmy Medical University(Third Military Medical University)Shigatse 857000China Department of RadiologyXiangyfa HospitalCentral South UniversityChangsha 410008China 

出 版 物：《Science China(Life Sciences)》 (中国科学（生命科学英文版）)

年 卷 期：2020年第63卷第12期

页      面：1879-1886页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81891002 and 81971178) the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16040700) the National Key Research and Development Program of China(2017YFA0104701,2017YFA0104704,2016YFC1101501 and 2016YFC1101502) 

主　　题：complete spinal cord injury allotransplantation adult spinal cord tissues(aSCTs) adult mammalian long-term survival functional restoration 

摘      要：Spinal cord injury(SCI), especially complete transected SCI, leads to loss of cells and extracellular matrix and functional impairments. In a previous study, we transplanted adult spinal cord tissues(aSCTs) to replace lost tissues and facilitate recovery in a rat SCI model. However, rodents display considerable differences from human patients in the scale, anatomy and functions of spinal cord systems, and responses after injury. Thus, use of a large animal SCI model is required to examine the repair efficiency of potential therapeutic approaches. In this study, we transplanted allogenic aSCTs from adult dogs to the lesion area of canines after complete transection of the thoracic spinal cord, and investigated the long-term cell survival and functional recovery. To enhance repair efficiency, a growth factor cocktail was added during aSCT transplantation, providing a favorable microenvironment. The results showed that transplantation of a SCTs, in particular with the addition of growth factors, significantly improves locomotor function restoration and increases the number of neurofilament-, microtubule-associated protein2-, 5-hydroxytryptamine-, choline acetyltransferase-and tyrosine hydroxylase-positive neurons in the lesion area at 6 months post-surgery. In addition, we demonstrated that donor neurons in a SCTs can survive for a long period after transplantation. This study showed for the first time that transplanting aSCTs combined with growth factor supplementation facilitates reconstruction of injured spinal cords, and consequently promotes long lasting motor function recovery in a large animal complete transected SCI model, and therefore could be considered as a possible therapeutic strategy in humans.