Effect of Wharton’s Jelly Derived Mesenchymal Stem Cells on the Expression of NLRP3 Receptor and Neuroinflammation in Experimental Spinal Cord Injury

Abstract

Introduction: The NOD-Like Receptor (NLR) family, pyrin domaincontaining protein 3 (NLRP3) inflammasome plays a major role in inflammation process. Structurally, the inflammasome consists of a receptor (NLRP3), an adaptor protein, and precursor of the enzyme caspase-1. Inflammasome activation in central nervous system injuries can activate caspase-1. This enzyme mediates the maturation and secretion of interleukin-1β (IL-1β) and IL-18, initiating inflammatory responses. Mesenchymal stem cells have shown immune modulation features and have been extensively used for treating inflammatory diseases. Aim: To investigate the effect of intracisternal transplantation of Wharton’s Jelly-Derived Mesenchymal stem Cells (WJMSCs) on the NLRP3 inflammasome in Spinal Cord Injury (SCI) rat model. Materials and Methods: Male wistar rats were divided into four groups (n=7) as following: laminectomy group, spinal cord injury group, vehicle group (the rats received phosphate-buffered saline), and WJMSCs treated group. Gene expression and protein production of NLRP3 receptor was evaluated by real time-PCR and western blotting. Serum concentration of IL-1β and IL-18 was measured by ELISA. Data were analysed using one-way ANOVA test followed by Tukey’s test. Results: The results showed that both gene and protein expressions of NLRP3 receptor were significantly increased in the SCI rats in comparison to the uninjured rats (p<0.05). In addition, the serum levels of IL-1β and IL-18 had upward trends in the SCI group compared to the laminectomy (p<0.05). On the other hand, WJMSCs significantly reversed the rises in both NLRP3 expression and interleukins amounts in comparison to the SCI group (p<0.05). Conclusion: It can be concluded that MSCs may modulate the inflammation process via inflammasome suppression.

Keywords

• inflammasome
• inflammation
• intracisternal transplantation