Intrathecal transplantation of Wharton’s jelly mesenchymal stem cells suppresses the NLRP1 inflammasome in the rat model of spinal cord injury

• Published in: Journal of chemical neuroanatomy 2019-04, Vol.97, p.1-8
• Main Authors: Mohamadi, Yousef, Noori Moghahi, Seyed Mohammad Hossein, Mousavi, Mahboubeh, Borhani-Haghighi, Maryam, Abolhassani, Farid, Kashani, Iraj Ragerdi, Hassanzadeh, Gholamreza
• Format: Article
• Language: English
• Subjects: Inflammasome; Intrathecal; Spinal cord injury; Transplantation; Wharton’s jelly mesenchymal stem cells
• ISSN: 0891-0618; 1873-6300
• DOI: 10.1016/j.jchemneu.2019.01.011

•Spinal cord injury (SCI) induced the activation of the NLRP1 inflammasome indicated by overexpression of the inflammasome components NLRP1, ASC, and caspase-1.•Intrathecal transplantation of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) suppressed the inflammasome and decreased the levels of pro-inflammatory cytokines IL-1β, IL-18, and TNF-α which resulted in the histologic and behavioral improvements.•Our data suggest that WJ-MSCs could improve the SCI, probably, through the downregulation of the pro-inflammatory cytokines following the inflammasome inactivation. After spinal cord injury (SCI) local inflammation is induced following secretion of interleukin-1beta (IL-1β) and IL-18. It has been described that the secretion of IL-1β and IL-18 is mediated by a cytoplasmic multiprotein complex, termed inflammasome. Mesenchymal stem cells (MSCs) have been extensively used for treating inflammatory diseases in which they showed immunomodulation characteristics. We utilized the anti-inflammatory potential of Wharton’s jelly mesenchymal stem cells (WJ-MSCs) to target inflammasome complex in rat SCI model. Real time-polymerase chain reaction, western blotting, and ELISA assay were done one week after SCI to measure the expression of the inflammasome components including NLRP1, ASC, and active caspase-1 as well as IL-1β, IL-18, and tumor necrosis factor-α (TNF-α). The histologic alteration and hind-limb locomotion were evaluated three weeks after injury by nissl staining and Basso, Beattie, Bresnahan (BBB), respectively. Our results showed that WJ-MSCs transplantation significantly decreased the SCI-induced expression of the evaluated factors in both mRNA and protein levels. In addition, WJ-MSCs significantly increased the number of normal-appearance neurons in the ventral horn of spinal cord. Noteworthy, these effects resulted in a significant improvement of motor function recovery. We conclude that inflammasome inhibition may be one of the mechanisms for the anti-inflammatory effect of MSCs in the SCI.