Abstract
Spinal cord injury (SCI) is caused by an external force, leading to severe dysfunction of the limbs below the injured segment. The inflammatory response plays a vital role in the prognosis of SCI. Human umbilical cord mesenchymal stem cell (hUCMSC) transplantation can promote repair of SCI by reducing the inflammatory response. We previously showed that hUCMSCs from 32 donors had different inhibitory abilities on BV2 cell proliferation. In this study, three experimental groups were established, and the mice were injected with different lines of hUCMSCs. Hind limb motor function, hematoxylin-eosin (H&E) staining, immunohistochemistry, Western blot (WB), qualitative real-time polymerase chain reaction (qRT-PCR), and RNA sequencing and correlation analysis were used to investigate the effects of hUCMSC transplantation on SCI mice and the underlying mechanisms. The results showed that the therapeutic effects of the three hUCMSC lines were positively correlated with their inhibitory abilities of BV2 cell proliferation rates in vitro. The MSC_A line had a better therapeutic effect on improving the hind limb motor function and greater effect on reducing the expression of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1) and increasing the expression of neuronal nuclei (NeuN). Differentially expressed genes including Zbtb16, Per3, and Hif3a were probably the key genes involved in the protective mechanism by MSC_A after nerve injury. qRT-PCR results further verified that Zbtb16, Per3, and Hif3a expressions reduced by SCI could be reversed by MSC_A application. These results suggest that the effect of hUCMSCs transplantation on acute SCI depends on their inhibitory abilities to inflammation reaction after nerve injury, which may help to shape future use of hUCMSCs combined with improving the effectiveness of clinical transformation.
Highlights
Spinal cord injury (SCI) is one of the most devastating central nervous system diseases and can cause severe nerve dysfunction and, at times, paralysis (Rogers and Todd, 2016)
The results showed that most of the cultured cells were positive for CD105, CD44, CD73, CD29, and CD166 proliferation rate of BV2 cells was detected after co-culturing expressions; they were negative for CD34, CD45, with the 32 lines of Human umbilical cord mesenchymal stem cell (hUCMSC) culture medium
The results in the present study showed that the neuronal nuclei (NeuN) protein level was significantly decreased, while the levels of glial fibrillary acidic protein (Gfap) and ionized calcium binding adaptor molecule 1 (Iba1) proteins were significantly increased after SCI (Figures 3A,B), which was consistent with previous results
Summary
Spinal cord injury (SCI) is one of the most devastating central nervous system diseases and can cause severe nerve dysfunction and, at times, paralysis (Rogers and Todd, 2016). The injury of the blood-spinal cord barrier after SCI induces neutrophils, monocytes, and macrophages to enter the injured spinal cord (Beck et al, 2010; Aubé et al, 2014; Gensel and Zhang, 2015; Jin et al, 2021). Many inflammatory factors are released, which further activate the microglia in damaged spinal cord tissues, triggering a severe local immune response. Controlling the activation of microglia and the resultant production of inflammatory factors may contribute to ameliorating the microenvironment of regeneration in SCI (Mizuno, 2011; Zhang et al, 2013)
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