title: Functionalized Collagen Scaffold Neutralizing the Myelin-Inhibitory Molecules Promoted Neurites Outgrowth in Vitro and Facilitated Spinal Cord Regeneration in Vivo.
abstract: Research has demonstrated that many myelin-associated inhibitory molecules jointly contribute to the failure of adult spinal cord regeneration. Therapies comprehensively targeting the multiple inhibitory nature of the injured spinal cord are being concerned. Here, two collagen-binding proteins, CBD-EphA4LBD and CBD-PlexinB1LBD, were constructed, respectively, to neutralize the axon guidance molecules ephrinB3 and sema4D that inhibit the regeneration of nerve fibers. The two neutralizing proteins have proven their ability to specifically bind collagen and to continuously release from collagen scaffolds. They could also promote neurites outgrowth of cerebellar granular neurons and dorsal root ganglion neurons in vitro. Subsequently, the functionalized collagen scaffolds by physically absorbing NEP1-40 and immobilizing CBD-EphA4LBD and CBD-PlexinB1LBD were transplanted into a rat T10 complete spinal cord transection model. Our results showed that rats that received the treatment of transplanting the functionalized collagen scaffold exhibited great advantage on axonal regeneration and locomotion recovery after spinal cord injury.
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.|§University of Chinese Academy of Sciences, Beijing 100190, China.
authors.forename: Xing
authors.initials: X
authors.lastname: Li
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Han
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Yannan
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: ‡Department of Biochemistry, Dalian Medical University, Dalian 116044, China.
authors.forename: Wenyong
authors.initials: W
authors.lastname: Ding
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianshu
authors.initials: J
authors.lastname: Wei
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Sufang
authors.initials: S
authors.lastname: Han
authors.affiliation: ‡Department of Biochemistry, Dalian Medical University, Dalian 116044, China.
authors.forename: Xianping
authors.initials: X
authors.lastname: Shang
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Bing
authors.initials: B
authors.lastname: Chen
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Zhifeng
authors.initials: Z
authors.lastname: Xiao
authors.affiliation: †State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
authors.forename: Jianwu
authors.initials: J
authors.lastname: Dai
mesh_terms: D000818:Animals; D003001:Cloning, Molecular; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D009186:Myelin Sheath / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins; D016501:Neurites / Q000187:drug effects* / Q000502:physiology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D036122:Receptor, EphA4 / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D058630:Spinal Cord Regeneration / Q000187:drug effects* / Q000502:physiology; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; C488752:Plxnb1 protein, rat; D011956:Receptors, Cell Surface; D011993:Recombinant Fusion Proteins; D003094:Collagen; D036122:Receptor, EphA4
keywords: collagen binding domain; functionalized collagen scaffold; myelin-inhibitory molecules; neutralizing protein; spinal cord injury