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Directed Neuronal Differentiation of Injury-activated Endogenous Neural Stem Cells for Acute Spinal Cord Injury Repair
Caixia Fan, Xing Li, Zhifeng Xiao, Yannan Zhao, Hui Liang, Bin Wang, Sufang Han, Xiaoran Li, Bai Xu, Nuo Wang, Sumei Liu, Weiei Xue, and Jianwu Dai
Acta Biomaterialia
Abstract
Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered collagen scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro. This fragment could also specifically bind to the collagen and undergo sustained release from collagen scaffold. Then, the scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified collagen scaffold could be an ideal candidate for spinal cord regeneration after acute SCI.
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论文编号: |
DOI:10.1016/j.actbio.2017.01.009 |
论文题目: |
Directed Neuronal Differentiation of Injury-activated Endogenous Neural Stem Cells for Acute Spinal Cord Injury Repair |
英文论文题目: |
Directed Neuronal Differentiation of Injury-activated Endogenous Neural Stem Cells for Acute Spinal Cord Injury Repair |
第一作者: |
Caixia Fan, Xing Li, Zhifeng Xiao, Yannan Zhao, Hui Liang, Bin Wang, Sufang Han, Xiaoran Li, Bai Xu, Nuo Wang, Sumei Liu, Weiei Xue, and Jianwu Dai |
英文第一作者: |
Caixia Fan, Xing Li, Zhifeng Xiao, Yannan Zhao, Hui Liang, Bin Wang, Sufang Han, Xiaoran Li, Bai Xu, Nuo Wang, Sumei Liu, Weiei Xue, and Jianwu Dai |
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2017-05-23 |
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摘要: |
Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered collagen scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro. This fragment could also specifically bind to the collagen and undergo sustained release from collagen scaffold. Then, the scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified collagen scaffold could be an ideal candidate for spinal cord regeneration after acute SCI. |
英文摘要: |
Due to irreversible neuronal loss and glial scar deposition, spinal cord injury (SCI) ultimately results in permanent neurological dysfunction. Neuronal regeneration of neural stem cells (NSCs) residing in the spinal cord could be an ideal strategy for replenishing the lost neurons and restore function. However, many myelin-associated inhibitors in the SCI microenvironment limit the ability of spinal cord NSCs to regenerate into neurons. Here, a linearly ordered collagen scaffold was used to prevent scar deposition, guide nerve regeneration and carry drugs to neutralize the inhibitory molecules. A collagen-binding EGFR antibody Fab fragment, CBD-Fab, was constructed to neutralize the myelin inhibitory molecules, which was demonstrated to promote neuronal differentiation and neurite outgrowth under myelin in vitro. This fragment could also specifically bind to the collagen and undergo sustained release from collagen scaffold. Then, the scaffolds modified with CBD-Fab were transplanted into an acute rat SCI model. The robust neurogenesis of endogenous injury-activated NSCs was observed, and these NSCs could not only differentiate into neurons but further mature into functional neurons to reconnect the injured gap. The results indicated that the modified collagen scaffold could be an ideal candidate for spinal cord regeneration after acute SCI. |
刊物名称: |
Acta Biomaterialia |
英文刊物名称: |
Acta Biomaterialia |
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其它备注: |
Caixia Fan, Xing Li, Zhifeng Xiao, Yannan Zhao, Hui Liang, Bin Wang, Sufang Han, Xiaoran Li, Bai Xu, Nuo Wang, Sumei Liu, Weiei Xue, and Jianwu Dai. Directed Neuronal Differentiation of Injury-activated Endogenous Neural Stem Cells for Acute Spinal Cord Injury Repair. Acta Biomaterialia. DOI: 10.1016/j.actbio.2017.01.009 |
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