Transplantation of olfactory ensheathing cells promotes the therapeutic effect of neural stem cells on spinal cord injury by inhibiting necrioptosis

Abstract Background: Neural stem cells (NSCs) transplantation has been considered as a potential strategy to reconnect the neural circuit after spinal cord injury (SCI) but the therapeutic effect was still unsatisfied because of the poor inflammatory microenvironment. Wnt4 has been considered to be neurogenesis and anti-inflammatory so that it would be an essential assistant agent for NSCs transplantation. To explore interaction between Wnt4-modified NSCs and macrophages; and the effect of Wnt4-modified NSCs on the inflammatory microenvironment of SCI is relevant for targeted and effective treatments that promote injured spinal cord repair. Methods: In vitro NSCs-macrophages co-cultured system was established to unravel the interaction and involved mechanism between Wnt4-modified NSCs and macrophages. Wnt4-modified NSCs were transplanted into SCI model to confirm the effect of Wnt4-modified NSCs on modulation of inflammatory microenvironment of SCI and the therapeutic effect of Wnt4-modified NSCs on SCI. Results: Wnt4-modified NSCs induce M2 polarization and inhibit M1 polarization of macrophages through suppress TLR4/NF-κB signal pathway; furthermore, M2 cells promote neuronal differentiation of NSCs through MAPK/JNK signal pathway. In vivo, transplantation of Wnt4-modified NSCs improve inflammatory microenvironment through induce M2 polarization and inhibit M1 polarization of macrophages to promote axonal regeneration and tissue repair.Conclusions: Transplantation of Wnt4-modified NSCs effectively improve the inflammatory microenvironment through inducing M2 polarization and suppressing M1 polarization of macrophages after SCI. Considering these positive therapeutic effects, Wnt4 may have remarkable potential to be optimal assistant agent in NSCs transplantation for SCI.

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Properties of Olfactory Ensheathing Cells Conditioned Medium and Its Potential Therapeutic Effect on Spinal Cord Injury: A Review

Medical Science Review ◽

10.12659/msrev.909751 ◽

2018 ◽

Vol 5 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Zhengchao Gao ◽

Yingjie Zhao ◽

Yiqun Wang ◽

Jiantao Liu ◽

Binbin Niu ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Conditioned Medium ◽

Therapeutic Effect ◽

Olfactory Ensheathing Cells ◽

Cord Injury ◽

Ensheathing Cells

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Therapeutic Potential of Olfactory Ensheathing Cells and Mesenchymal Stem Cells in Spinal Cord Injuries

Stem Cells International ◽

10.1155/2017/3978595 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 19

Author(s):

Zadroga Anna ◽

Jezierska-Woźniak Katarzyna ◽

Czarzasta Joanna ◽

Monika Barczewska ◽

Wojtkiewicz Joanna ◽

...

Keyword(s):

Spinal Cord ◽

Stem Cells ◽

Spinal Cord Injury ◽

Mesenchymal Stem Cells ◽

Spinal Cord Injuries ◽

Therapeutic Potential ◽

Current Knowledge ◽

Olfactory Ensheathing Cells ◽

Cord Injury ◽

Ensheathing Cells

Spinal cord injury (SCI) is a devastating neurological condition that affects individuals worldwide, significantly reducing quality of life, for both patients and their families. In recent years there has been a growing interest in cell therapy potential in the context of spinal cord injuries. The present review aims to discuss and compare the restorative approaches based on the current knowledge, available spinal cord restorative cell therapies, and use of selected cell types. However, treatment options for spinal cord injury are limited, but rehabilitation and experimental technologies have been found to help maintain or improve remaining nerve function in some cases. Mesenchymal stem cells as well as olfactory ensheathing cells seem to show therapeutic impact on damaged spinal cord and might be useful in neuroregeneration. Recent research in animal models and first human trials give patients with spinal cord injuries hope for recovery.

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