Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers

Yi Xiong1,*, Ji-Xiang Zhu2,*, Zheng-Yu Fang1, Cheng-Guang Zeng2, Chao Zhang1, Guo-Long Qi3, Man-Hui Li1, Wei Zhang1, Da-Ping Quan2, Jun Wan1,41Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, 2DSAPM Lab, PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemi...

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Autores principales: Xiong Y, Zhu JX, Fang ZY, Zeng CG, Zhang C, Qi GL, Li MH, Zhang W, Quan DP, Wan J
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Publicado: Dove Medical Press 2012
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spelling oai:doaj.org-article:e51d436910ea4134a82bac96fbebc2162021-12-02T05:09:47ZCoseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers1176-91141178-2013https://doaj.org/article/e51d436910ea4134a82bac96fbebc2162012-04-01T00:00:00Zhttp://www.dovepress.com/coseeded-schwann-cells-myelinate-neurites-from-differentiated-neural-s-a9698https://doaj.org/toc/1176-9114https://doaj.org/toc/1178-2013Yi Xiong1,*, Ji-Xiang Zhu2,*, Zheng-Yu Fang1, Cheng-Guang Zeng2, Chao Zhang1, Guo-Long Qi3, Man-Hui Li1, Wei Zhang1, Da-Ping Quan2, Jun Wan1,41Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, 2DSAPM Lab, PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 3Department of Medical Information, Medical Collage of Jinan University, Guangzhou, 4Division of Life Science, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China*These authors contributed equally to this manuscriptAbstract: 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.Keywords: PLGA, NT-3, neural stem cells, Schwann cells, myelin sheathXiong YZhu JXFang ZYZeng CGZhang CQi GLLi MHZhang WQuan DPWan JDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2012, Iss default, Pp 1977-1989 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine (General)
R5-920
spellingShingle Medicine (General)
R5-920
Xiong Y
Zhu JX
Fang ZY
Zeng CG
Zhang C
Qi GL
Li MH
Zhang W
Quan DP
Wan J
Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers
description Yi Xiong1,*, Ji-Xiang Zhu2,*, Zheng-Yu Fang1, Cheng-Guang Zeng2, Chao Zhang1, Guo-Long Qi3, Man-Hui Li1, Wei Zhang1, Da-Ping Quan2, Jun Wan1,41Biomedical Research Institute, Shenzhen-PKU-HKUST Medical Center, Shenzhen, 2DSAPM Lab, PCFM Lab, Institute of Polymer Science, School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou, 3Department of Medical Information, Medical Collage of Jinan University, Guangzhou, 4Division of Life Science, the Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, People's Republic of China*These authors contributed equally to this manuscriptAbstract: 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.Keywords: PLGA, NT-3, neural stem cells, Schwann cells, myelin sheath
format article
author Xiong Y
Zhu JX
Fang ZY
Zeng CG
Zhang C
Qi GL
Li MH
Zhang W
Quan DP
Wan J
author_facet Xiong Y
Zhu JX
Fang ZY
Zeng CG
Zhang C
Qi GL
Li MH
Zhang W
Quan DP
Wan J
author_sort Xiong Y
title Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers
title_short Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers
title_full Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers
title_fullStr Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers
title_full_unstemmed Coseeded Schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded PLGA carriers
title_sort coseeded schwann cells myelinate neurites from differentiated neural stem cells in neurotrophin-3-loaded plga carriers
publisher Dove Medical Press
publishDate 2012
url https://doaj.org/article/e51d436910ea4134a82bac96fbebc216
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