Journal
BIOMATERIALS
Volume 237, Issue -, Pages -Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.biomaterials.2020.119830
Keywords
Photo-crosslinked gelatin hydrogel; Microglia/macrophages; Inflammation; Neurogenesis; Complete transection spinal cord injury (SCI)
Funding
- National Natural Science Foundation of China [81891002, 81891003, 81971178]
- Strategic Priority Research Program of the Chinese Academy of Sciences [XDA16040700]
- National Key Research and Development Program of China [2016YFC1101501, 2016YFC1101502, 2017YFA0104701, 2017YFA0104704]
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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.
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