Adipose‐derived mesenchymal stem cells overexpressing prion improve outcomes via the NLRP3 inflammasome/DAMP signalling after spinal cord injury in rat. Issue 4 (20th January 2023)

• Record Type: Journal Article
• Authors: Yin, Tsung‐Cheng; Li, Yi‐Chen; Sung, Pei‐Hsun; Chiang, John Y.; Shao, Pei‐Lin; Yip, Hon‐Kan; Lee, Mel S.
• Is Part Of: Journal of cellular and molecular medicine. Volume 27:Issue 4(2023)
• Page Start: 482
• Page End: 495
• Publication Date: 2023-01-20
• Subjects: adipose‐derived mesenchymal stem cells -- inflammasome -- inflammatory signalling -- prion protein -- spinal cord injury; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.17620
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: Traumatic spinal cord injury (SCI) is a highly destructive disease in human neurological functions. Adipose‐derived mesenchymal stem cells (ADMSCs) have tissue regenerations and anti‐inflammations, especially with prion protein overexpression (PrPc OE ). Therefore, this study tested whether PrPc OE ‐ADMSCs therapy offered benefits in improving outcomes via regulating nod‐like‐receptor‐protein‐3 (NLRP3) inflammasome/DAMP signalling after acute SCI in rats. Compared with ADMSCs only, the capabilities of PrPc OE ‐ADMSCs were significantly enhanced in cellular viability, anti‐oxidative stress and migration against H2 O2 and lipopolysaccharide damages. Similarly, PrPc OE ‐ADMSCs significantly inhibited the inflammatory patterns of Raw264.7 cells. The SD rats ( n = 32) were categorized into group 1 (Sham‐operated‐control), group 2 (SCI), group 3 (SCI + ADMSCs) and group 4 (SCI + PrPc OE ‐ADMSCs). Compared with SCI group 2, both ADMSCs and PrPc OE ‐ADMSCs significantly improved neurological functions. Additionally, the circulatory inflammatory cytokines levels (TNF‐α/IL‐6) and inflammatory cells (CD11b/c+/MPO+/Ly6G+) were highest in group 2, lowest in group 1, and significantly higher in group 3 than in group 4. By Day 3 after SCI induction, the protein expressions of inflammasome signalling (HGMB1/TLR4/MyD88/TRIF/c‐caspase8/FADD/p‐NF‐κB/NEK7/NRLP3/ASC/c‐caspase1/IL‐ß) and by Day 42 the protein expressions of DAMP‐inflammatory signalling (HGMB1/TLR‐4/MyD88/TRIF/TRAF6/p‐NF‐κB/TNF‐α/IL‐1ß) in spinal cord tissues displayed an identical pattern as the inflammatory patterns. In conclusion, PrPc OE ‐ADMSCs significantly attenuated SCI in rodents that could be through suppressing the inflammatory signalling.