Transplantation of Wnt5a-modified NSCs promotes tissue repair and locomotor functional recovery after spinal cord injury

Abstract

Traditional therapeutic strategies for spinal cord injury (SCI) are insufficient to repair locomotor function because of the failure of axonal reconnection and neuronal regeneration in the injured central nervous system (CNS). Neural stem cell (NSC) transplantation has been considered a potential strategy and is generally feasible for repairing the neural circuit after SCI; however, the most formidable problem is that the neuronal differentiation rate of NSCs is quite limited. Therefore, it is essential to induce the neuronal differentiation of NSCs and improve the differentiation rate of NSCs in spinal cord repair. Our results demonstrate that both Wnt5a and miRNA200b-3p could promote NSC differentiation into neurons and that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling to promote NSC differentiation into neurons. Wnt5a could reduce RhoA expression by upregulating miRNA200b-3p expression to inhibit activation of the RhoA/Rock signaling pathway, which has been reported to suppress neuronal differentiation. Overexpression of RhoA abolished the neurogenic capacity of Wnt5a and miRNA200b-3p. In vivo, miRNA200b-3p was critical for Wnt5a-induced NSC differentiation into neurons to promote motor functional and histological recovery after SCI by suppressing RhoA/Rock signaling. These findings provide more insight into SCI and help with the identification of novel treatment strategies.

LINGO-1 regulates Wnt5a signaling during neural stem and progenitor cell differentiation by modulating miR-15b-3p levels

“…Jang et al discovered that Wnt5a could activate neural differentiation by activating the Wnt5a/JNK pathway [ 23 ]. Li et al also found that Wnt5a could promote NSC differentiation into neurons and further revealed that Wnt5a upregulated miRNA200b-3p expression through MAPK/JNK signaling, which was in accordance with our study [ 24 ]. In our study, we demonstrated that the expression of Wnt5a and p-JNK increased significantly during the differentiation of sp-NSPCs after LINGO-1 shRNA treatment, whereas the canonical Wnt pathway factor β-catenin did not change.…”

Trends of Chitosan Based Delivery Systems in Neuroregeneration and Functional Recovery in Spinal Cord Injuries

“…NSCs are isolated from the subventricular zone of the hippocampus of the brain and a region of the central canal of the spinal cord and can differentiate into specific neuronal or glial phenotypes to replace lost tissue or produce pro-regenerative factors. Transplantation of NSCs into the lesioned spinal cord leads to functional recovery, sustained through neuronal cell replacement that was able to reconstitute lost neuronal and glial tissue with trophic support (BDNF, CNTF, GDNF, NGF, and IGF-1) preserving damaged cells and axons [22]. Studies have shown the immunomodulatory activities of NSCs that can be helpful in the treatment of SCI [23].…”

Transplantation of Wnt4-modified Neural Stem Cells Mediate M2 Polarization to Promote Spinal Cord Injury Repair

“…To elicit a SCEP, a single pulse stimulation (50 ms in duration at a frequency of 5.1 Hz and a voltage increase of 1 mV) was transmitted through the electrodes until a mild twitch of the vertebral body of the animal was observed. One hundred SCEP responses were averaged for each rat to obtain high-quality waveforms for the SCEP signals [32].…”

“…To visualize the cavity area, animals (n = 5 per group) were killed for haematoxylin-eosin (HE) staining. The T8-T11 longitudinal spinal cord sections from each group were stained with HE according to standard protocols and observed under bright eld microscope [22,32].…”