A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair

Fan, Cunyi; Li, Xing; Xiao, Zhifeng; Zhao, Yannan; Liang, Hui; Wang, Bin; Han, Sufang; Li, Xiaoran; Bai, Xu; Wang, Nuo; Liu, Sumei; Xue, Weiwei; Dai, Jianwu

doi:10.1016/j.actbio.2017.01.009

Cited by 125 publications

(107 citation statements)

References 55 publications

Supporting

Mentioning

103

Contrasting

Unclassified

Order By: Relevance

“…The lack of contact guidance makes the processes of nerve regeneration at the spinal cord injury site disordered and blind, and crossing the injury zone, the axons can hardly reach the distal end. The formation of glial scar at the local site was an obstacle to the extension of the nerve . As we expected, the regenerated nerve fibers extended in an ordered direction in the collagen scaffolds, and there were more ordered NF‐positive nerve fibers at the injury site in the CS/CBD‐VEGF group than in the control and CS groups.…”

Section: Discussionsupporting

confidence: 50%

Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor‐targeting collagen scaffold

Wang

Shi

et al. 2017

Journal Orthopaedic Research

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) is global health concern. The effective strategies for SCI are relevant to the improvement on nerve regeneration microenvironment. Vascular endothelial growth factor (VEGF) is an important cytokine for inducing angiogenesis and accelerating nerve system function recovery from injury. We proposed that VEGF could improve nerve regeneration in SCI. However, an uncontrolled delivery system target to injury site not only decreases the therapeutic efficacy but also increases the risk of tumor information. We implanted collagen scaffold (CS) targeted with a constructed protein, collagen-binding VEGF (CBD-VEGF), to bridge transected spine cord gap in a rat transected SCI model. Functional and histological examinations were conducted to assess the repair capacity of the delivery system CS/CBD-VEGF. The results indicated that the implantation of CS/CBD-VEGF into the model rats improved the survival rate and exerted beneficial effect on functional recovery. The controlled intervention improved the microenvironment, guided axon growth, and promoted neovascularization at the injury site. Therefore, the delivery system with stable binding of VEGF potentially provides a better therapeutic option for SCI. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1024-1034, 2018.

show abstract

Section: Discussionsupporting

confidence: 50%

Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor‐targeting collagen scaffold

Wang

Shi

et al. 2017

Journal Orthopaedic Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…Female adult SD rats (210‐230 g) were used for surgery. Animals were anesthetized by intraperitoneal (ip) injection of chloral hydrate (0.5 g/kg) before surgery according to previous protocol . Two surgical models were used: (1) complete spinal cord injury between thoracic 8 and 9 (T8‐T9); (2) intraspinal injection.…”

Section: Methodsmentioning

confidence: 99%

Vascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury

Liu

Xiao

et al. 2018

CNS Neurosci Ther

Self Cite

View full text Add to dashboard Cite

In vitro, VEGF triggered spinal cord NSCs proliferation and maintained self-renewal. Further investigations demonstrated VEGF transactivated epidermal growth factor receptor (EGFR) through VEGF receptor 2 (VEGFR2) to promote spinal cord NSCs proliferation. In vivo, we injected VEGF into spinal cord by laminectomy to confirm the roles of VEGF-VEGFR2-EGFR signals in NSCs activation. VEGF significantly elevated the number of activated NSCs and increased EGFR phosphorylation. In contrast, intraspinal injection of specific inhibitors targeting EGFR and VEGFR2 decreased NSCs activation after SCI. Our results demonstrate that VEGF-VEGFR2-EGFR axis is important for NSCs activation after SCI, providing new insights into the mechanisms of spinal cord NSCs activation postinjury.

show abstract

“…The NeuroRegen scaffold combined with CBD-EGFR-Fab prevented the inhibition of neuronal differentiation of cultured NSCs by myelin. 6,10 Collagen scaffolds modified with anti-EGFR antibody promote neuronal differentiation in animal models of SCI To evaluate the therapeutic effects of the collagen scaffold modified with anti-EGFR antibody in SCI, we established rat and canine models of complete spinal cord transection. Unlike previous models of SCI that used contusion, compression, dislocation or partial transection, our SCI model had a gap in the spinal cord-the spinal cord was completely separated and no spinal cord tissue was left in the lesion site.…”

Section: Collagen Scaffolds Modified With Anti-egfr Antibody Prevent mentioning

confidence: 99%

“…2,3 After SCI, quiescent NSCs are activated and migrate toward the injury site. [4][5][6] Neuronal differentiation of NSCs residing in the spinal cord is regarded as a promising strategy for replenishing lost neurons after SCI. However, endogenous and exogenous transplanted NSCs rarely differentiate into neurons; they primarily differentiate into astrocytes and thus contribute to formation of a glial scar in the injury site, which greatly affects the therapeutic efficacy of NSCs for SCI repair.…”

Section: Introductionmentioning

confidence: 99%

“…Our studies have revealed that a collagen scaffold modified with an antiepidermal growth factor receptor (EGFR) antibody was able to rebuild a regenerative microenvironment that promoted neuronal differentiation of NSCs; the nascent neurons formed neuronal relays for SCI repair. 6,[10][11][12] Here, we summarize related research to highlight the importance of the neuronal differentiation microenvironment for SCI repair.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The neuronal differentiation microenvironment is essential for spinal cord injury repair

2017

Self Cite

View full text Add to dashboard Cite

Spinal cord injury (SCI) often leads to substantial disability due to loss of motor function and sensation below the lesion. Neural stem cells (NSCs) are a promising strategy for SCI repair. However, NSCs rarely differentiate into neurons; they mostly differentiate into astrocytes because of the adverse microenvironment present after SCI. We have shown that myelin-associated inhibitors (MAIs) inhibited neuronal differentiation of NSCs. Given that MAIs activate epidermal growth factor receptor (EGFR) signaling, we used a collagen scaffold-tethered anti-EGFR antibody to attenuate the inhibitory effects of MAIs and create a neuronal differentiation microenvironment for SCI repair. The collagen scaffold modified with anti-EGFR antibody prevented the inhibition of NSC neuronal differentiation by myelin. After transplantation into completely transected SCI animals, the scaffold-linked antibodies induced production of nascent neurons from endogenous and transplanted NSCs, which rebuilt the neuronal relay by forming connections with each other or host neurons to transmit electrophysiological signals and promote functional recovery. Thus, a scaffold-based strategy for rebuilding the neuronal differentiation microenvironment could be useful for SCI repair.

show abstract

A modified collagen scaffold facilitates endogenous neurogenesis for acute spinal cord injury repair

Cited by 125 publications

References 55 publications

Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor‐targeting collagen scaffold

Increased vascularization promotes functional recovery in the transected spinal cord rats by implanted vascular endothelial growth factor‐targeting collagen scaffold

Vascular endothelial growth factor activates neural stem cells through epidermal growth factor receptor signal after spinal cord injury

The neuronal differentiation microenvironment is essential for spinal cord injury repair

Contact Info

Product

Resources

About