title: Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers.
abstract: Biomaterials and neurotrophic factors represent promising guidance for neural repair. In this study, we combined poly-(lactic acid-co-glycolic acid) (PLGA) conduits and neurotrophin-3 (NT-3) to generate NT-3-loaded PLGA carriers in vitro. Bioactive NT-3 was released stably and constantly from PLGA conduits for up to 4 weeks. Neural stem cells (NSCs) and Schwann cells (SCs) were coseeded into an NT-releasing scaffold system and cultured for 14 days. Immunoreactivity against Map2 showed that most of the grafted cells (>80%) were differentiated toward neurons. Double-immunostaining for synaptogenesis and myelination revealed the formation of synaptic structures and myelin sheaths in the coculture, which was also observed under electron microscope. Furthermore, under depolarizing conditions, these synapses were excitable and capable of releasing synaptic vesicles labeled with FM1-43 or FM4-64. Taken together, coseeding NSCs and SCs into NT-3-loaded PLGA carriers increased the differentiation of NSCs into neurons, developed synaptic connections, exhibited synaptic activities, and myelination of neurites by the accompanying SCs. These results provide an experimental basis that supports transplantation of functional neural construction in spinal cord injury.
authors.affiliation: Biomedical Research Institute, Shenzhen- PKU-HKUST Medical Center, Shenzhen, People’s Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xiong
authors.forename: Ji-Xiang
authors.initials: JX
authors.lastname: Zhu
authors.forename: Zheng-Yu
authors.initials: ZY
authors.lastname: Fang
authors.forename: Cheng-Guang
authors.initials: CG
authors.lastname: Zeng
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Guo-Long
authors.initials: GL
authors.lastname: Qi
authors.forename: Man-Hui
authors.initials: MH
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Da-Ping
authors.initials: DP
authors.lastname: Quan
authors.forename: Jun
authors.initials: J
authors.lastname: Wan
mesh_terms: D000818:Animals; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D004337:Drug Carriers; D019344:Lactic Acid; D046529:Microscopy, Electron, Transmission; D009186:Myelin Sheath / Q000187:drug effects / Q000502:physiology; D050997:Nanomedicine; D009413:Nerve Fibers, Myelinated / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D058953:Neural Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D016501:Neurites / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D020933:Neurotrophin 3 / Q000008:administration & dosage*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D051381:Rats; D012583:Schwann Cells / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000648:ultrastructure; D054457:Tissue Scaffolds / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D020933:Neurotrophin 3; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid