A novel hydrogel-based treatment for complete transection spinal cord injury repair is driven by microglia/macrophages repopulation

Microglia/macrophage mediated-inflammation, a main contributor to the microenvironment after spinal cord injury (SCI), persists for a long period of time and affects SCI repair. However, the effects of microglia/macrophage mediated-inflammation on neurogenic differentiation of endogenous neural stem...

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Bibliographic Details
Published in:Biomaterials 2020-04, Vol.237, p.119830-119830, Article 119830
Main Authors: Ma, Dezun, Zhao, Yannan, Huang, Lei, Xiao, Zhifeng, Chen, Bing, Shi, Ya, Shen, He, Dai, Jianwu
Format: Article
Language:English
Subjects:
Animals
Complete transection spinal cord injury (SCI)
Hydrogels
Inflammation
Macrophages
Mice
Mice, Inbred C57BL
Microglia
Microglia/macrophages
Neurogenesis
Photo-crosslinked gelatin hydrogel
Spinal Cord
Spinal Cord Injuries - therapy
Spinal Cord Regeneration
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Summary:Microglia/macrophage mediated-inflammation, a main contributor to the microenvironment after spinal cord injury (SCI), persists for a long period of time and affects SCI repair. However, the effects of microglia/macrophage mediated-inflammation on neurogenic differentiation of endogenous neural stem/progenitor cells (NSPCs) are not well understood. In this study, to attenuate activated microglia/macrophage mediated-inflammation in the spinal cord of complete transection SCI mice, a combination of photo-crosslinked hydrogel transplantation and CSF1R inhibitor (PLX3397) treatment was used to replace the prolonged, activated microglia/macrophages via cell depletion and repopulation. This combined treatment in SCI mice produced a significant reduction in CD68-positive reactive microglia/macrophages and mRNA levels of pro-inflammatory factors, and a substantial increase in the number of Tuj1-positive neurons in the lesion area compared with single treatment methods. Moreover, most of the newborn Tuj1-positive neurons were confirmed to be generated from endogenous NSPCs using a genetic fate mapping mouse line (Nestin-CreERT2; LSL-tdTomato) that can label and trace NSPC marker-nestin expressing cells and their progenies. Collectively, our findings show that the combined treatment method for inhibiting microglia/macrophage mediated-inflammation promotes endogenous NSPC neurogenesis and improves functional recovery, which provides a promising therapeutic strategy for complete transection SCI.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2020.119830