Abstract
Background: This study employed a severed finger rat model to analyze the effects of human mesenchymal stem cells (MSCs) on angiogenesis, inflammatory response, apoptosis, and oxidative stress, to evaluate the possible mechanism of the repair effect of MSCs on severed finger (SF) rats.
Methods: Sixty Sprague-Dawley (SD) rats were categorized into five groups (n = 12). The pathological changes of severed finger tissues were investigated by Hematoxylin and eosin (H&E) staining on day 14 after the rats were sacrificed. The levels of inflammatory factors and oxidative stress factors were detected by ELISA. Terminal Deoxynucleotidyl Transferase (TdT) dUTP Nick End Labeling (TUNEL) was employed to assess the apoptosis of chondrocytes in severed finger tissues. The expression of osteocalcin (OCN), osteopontin (OPN), Collagen I (Col-1), and CD31 were detected by immunohistochemistry or immunofluorescence assay, respectively. The expression levels of related proteins were determined by western blot.
Result: Our study presented evidence that MSCs treatment improved pathological changes of skin and bone tissue, diminished the inflammatory response, prevented oxidative stress injury, suppressed chondrocyte apoptosis, and promoted angiogenesis, and bone formation compared to the model group. In addition, EX527 treatment attenuated the effect of MSCs, SRT1720 and ML385 co-treatment also attenuated the effect of MSCs. Importantly, the MSCs treatment increased the expression of Sirtuin 1(SIRT1)/Nuclear factor erythroid2-related factor 2(Nrf2) relate proteins.
Conclusion: Our study indicated that the mechanism of the effect of MSCs on a severed finger was related to the SIRT1/ Nrf2 signaling pathway.
Graphical Abstract
[http://dx.doi.org/10.1038/s41467-020-17404-0] [PMID: 32678102]
[http://dx.doi.org/10.1126/science.aam7928] [PMID: 28596335]
[http://dx.doi.org/10.1038/nri2395] [PMID: 19172693]
[http://dx.doi.org/10.3390/cells10040901] [PMID: 33919910]
[http://dx.doi.org/10.1155/2020/5924983] [PMID: 32399043]
[http://dx.doi.org/10.1002/sctm.17-0129] [PMID: 29076267]
[http://dx.doi.org/10.1089/ars.2017.7290] [PMID: 28891317]
[http://dx.doi.org/10.1016/j.jare.2021.06.023] [PMID: 35024180]
[http://dx.doi.org/10.1016/j.yexcr.2017.09.042] [PMID: 28986066]
[http://dx.doi.org/10.1016/j.taap.2015.12.024] [PMID: 26747300]
[http://dx.doi.org/10.1038/cddis.2016.3] [PMID: 26866273]
[http://dx.doi.org/10.3389/fimmu.2021.770744] [PMID: 34899720]
[http://dx.doi.org/10.1016/j.biopha.2018.09.035] [PMID: 30216799]
[http://dx.doi.org/10.2147/DDDT.S247103] [PMID: 32546964]
[http://dx.doi.org/10.1016/j.bjps.2020.08.077] [PMID: 32948497]
[http://dx.doi.org/10.1007/s11011-015-9659-z] [PMID: 25761767]
[http://dx.doi.org/10.1016/j.biomaterials.2012.02.042] [PMID: 22425554]
[http://dx.doi.org/10.1016/j.jpurol.2019.03.003] [PMID: 30967358]
[http://dx.doi.org/10.1007/s11926-000-0082-y] [PMID: 11123062]
[http://dx.doi.org/10.3390/ijms20061323] [PMID: 30875984]
[http://dx.doi.org/10.1161/ATVBAHA.121.317295] [PMID: 35296150]
[http://dx.doi.org/10.1016/j.ab.2016.10.021] [PMID: 27789233]
[http://dx.doi.org/10.1155/2021/6116890] [PMID: 34512868]
[http://dx.doi.org/10.1155/2020/8076105] [PMID: 32089781]
[http://dx.doi.org/10.1186/s12951-021-00940-2] [PMID: 34193158]
[http://dx.doi.org/10.1128/IAI.01618-13] [PMID: 24566623]
[http://dx.doi.org/10.1007/s12199-010-0181-y] [PMID: 21431799]
[http://dx.doi.org/10.1186/1471-2474-14-18] [PMID: 23302451]
[http://dx.doi.org/10.1039/C7BM00695K] [PMID: 29167844]
[http://dx.doi.org/10.3390/mi12080927] [PMID: 34442549]