Volume 26, Issue 2 (June 2022)                   Physiol Pharmacol 2022, 26(2): 200-212 | Back to browse issues page

XML Print

Download citation:
BibTeX | RIS | EndNote | Medlars | ProCite | Reference Manager | RefWorks
Send citation to:
Zafarmand S S, Salehi M S, Mokhtari M J, Safari A, Pandamooz S, Dianatpour M et al . Acetylsalicylic acid enhanced neurotrophic profile of epidermal neural crest stem cells: a possible approach for the combination therapy. Physiol Pharmacol 2022; 26 (2) :200-212
URL: http://ppj.phypha.ir/article-1-1760-en.html
Acetylsalicylic acid enhanced neurotrophic profile of epidermal neural crest stem cells: a possible approach for the combination therapy
Seyedeh Shaghayegh Zafarmand , Mohammad Saied Salehi , Mohammad Javad Mokhtari , Anahid Safari , Sareh Pandamooz , Mehdi Dianatpour , Afshin Borhani-Haghighi
Abstract:   (1664 Views)
Introduction: Stem cell therapy is considered as a promising strategy to treat neurological disorders. Amongst different cell types that are recruited under these devastating conditions, epidermal neural crest stem cells (EPI-NCSCs) are known as potential candidates. Acetylsalicylic acid (ASA or aspirin) is one of the commonly prescribed drugs that might affect the therapeutic potential of the transplanted stem cells. Hence, the present study aimed to evaluate the effects of ASA on the expression of fundamental growth factors involved in restorative pathways expressed by EPI-NCSCs in vitro for possible combination therapy’s purpose. Methods: EPI-NCSCs were obtained from the rat’s hair follicle. The appropriate ASA concentration to treat the cells was defined based on the MTT assay and then the obtained cells were treated with 80 or 800µM ASA for 1, 3 or 7 days. The relative expressions of Bdnf, Gdnf, Ngf, Neurotrophin-3, Vegf, Gfap, and doublecortin were finally assessed by qRT-PCR. Results: The obtained data revealed that the growth factors expressions are influenced by concentration and duration of the treatment applied. One-day ASA treatment was found to be able to increase the expression of all the evaluated genes, except Gdnf and doublecortin, which elevated three days later. Herein, seven-day treatment of stem cells with 800µM ASA resulted in higher levels of Bdnf, Vegf, and doublecortin.
Conclusion: Therefore, combination of aspirin and EPI-NCSCs might increase the therapeutic potential of these stem cells to treat neurological disorders.
Keywords: Aspirin, ASA, EPI-NCSCs, Growth factors, Neurological disorders
Full-Text [PDF 2781 kb]   (385 Downloads)    
Type of Manuscript: Experimental research article | Subject: Cell, Stem Cell and Cancer
References
1. Abd Rahman F, Mohd Ali J, Abdullah M, Abu Kasim NH, Musa S. Aspirin enhances osteogenic potential of periodontal ligament stem cells (pdlscs) and modulates the expression profile of growth factor-associated genes in pdlscs. J Periodontol 2016; 87: 837-47. [DOI:10.1902/jop.2016.150610]
2. Aloe L, Rocco ML, Bianchi P, Manni L. Nerve growth factor: From the early discoveries to the potential clinical use. J Transl Med 2012; 10: 1-5. [DOI:10.1186/1479-5876-10-239]
3. Baharvand Z, Nabiuni M, Tahmaseb M, Amini E, Pandamooz S. Investigating the synergic effects of valproic acid and crocin on bdnf and gdnf expression in epidermal neural crest stem cells. Acta Neurobiol Exp 2020; 80: 38-46. [DOI:10.21307/ane-2020-004]
4. Bhattacharyya M, Karmohapatra SK, Bhattacharya G, Bhattacharya R, Sinha AK. The role of leucocytes in the acetyl salicylic acid (aspirin) induced nitric oxide synthesis in the production of interferon-α, a potent inhibitor of platelet aggregation and a thrombolytic agent. J Thromb Thrombolysis 2009; 28: 173-84. [DOI:10.1007/s11239-008-0283-1]
5. Brenner M. Role of gfap in cns injuries. Neurosci Lett 2014; 565: 7-13. [DOI:10.1016/j.neulet.2014.01.055]
6. Choucry AM, Al-Shorbagy MY. Pharmacological manipulation of trk, p75ntr, and ngf balance restores memory deficit in global ischemia/reperfusion model in rats. J Mol Neurosci 2019; 68: 78-90. [DOI:10.1007/s12031-019-01284-1]
7. Curcio M, Salazar IL, Inacio AR, Duarte EP, Canzoniero LM, Duarte CB. Brain ischemia downregulates the neuroprotective gdnf-ret signaling by a calpain-dependent mechanism in cultured hippocampal neurons. Cell Death Dis 2015; 6: e1645. [DOI:10.1038/cddis.2014.578]
8. Dikshit P, Chatterjee M, Goswami A, Mishra A, Jana NR. Aspirin induces apoptosis through the inhibition of proteasome function. J Biol Chem 2006; 281: 29228-35. [DOI:10.1074/jbc.M602629200]
9. Divani AA, Zantek ND, Borhani-Haghighi A, Rao GH. Antiplatelet therapy: Aspirin resistance and all that jazz! Clin Appl Thromb Hemost 2013; 19: 5-18. [DOI:10.1177/1076029612449197]
10. Esmaeilzade B, Nobakht M, Joghataei MT, Roshandel NR, Rasouli H, Kuchaksaraei AS, et al. Delivery of epidermal neural crest stem cells (epi-ncsc) to hippocamp in alzheimer's disease rat model. Iran Biomed J 2012; 16: 1.
11. Gao F, Chiu SM, Motan DA, Zhang Z, Chen L, Ji HL, et al. Mesenchymal stem cells and immunomodulation: Current status and future prospects. Cell Death Dis 2016; 7: e2062. [DOI:10.1038/cddis.2015.327]
12. Gericota B, Anderson JS, Mitchell G, Borjesson DL, Sturges BK, Nolta JA, et al. Canine epidermal neural crest stem cells: Characterization and potential as therapy candidate for a large animal model of spinal cord injury. Stem Cells Transl Med 2014; 3: 334-45. [DOI:10.5966/sctm.2013-0129]
13. Hao W, Shi S, Zhou S, Wang X, Nie S. Aspirin inhibits growth and enhances cardiomyocyte differentiation of bone marrow mesenchymal stem cells. Eur J Pharmacol 2018; 827: 198- 207. [DOI:10.1016/j.ejphar.2018.03.016]
14. Hu YF, Gourab K, Wells C, Clewes O, Schmit BD, Sieber-Blum M. Epidermal neural crest stem cell (epi-ncsc)-mediated recovery of sensory function in a mouse model of spinal cord injury. Stem Cell Rev Rep 2010; 6: 186-98. [DOI:10.1007/s12015-010-9152-3]
15. Hu YF, Zhang ZJ, Sieber‐Blum M. An epidermal neural crest stem cell (epi‐ncsc) molecular signature. Stem Cells 2006; 24: 2692-702. [DOI:10.1634/stemcells.2006-0233]
16. Hua R, Doucette R, Walz W. Doublecortin-expressing cells in the ischemic penumbra of a small-vessel stroke. J Neurosci Res 2008; 86: 883-93. [DOI:10.1002/jnr.21546]
17. Hwang M, Park HH, Choi H, Lee KY, Lee YJ, Koh S-H. Effects of aspirin and clopidogrel on neural stem cells. Cell Biol Toxicol 2018; 34: 219-32. [DOI:10.1007/s10565-017-9412-y]
18. Jin M, Li C, Zhang Q, Xing S, Kan X, Wang J. Effects of aspirin on proliferation, invasion and apoptosis of hep-2 cells via the pten/akt/nf-kappab/survivin signaling pathway. Oncol Lett 2018; 15: 8454-60. [DOI:10.3892/ol.2018.8377]
19. Kellner Y, Godecke N, Dierkes T, Thieme N, Zagrebelsky M, Korte M. The bdnf effects on dendritic spines of mature hippocampal neurons depend on neuronal activity. Front Synaptic Neurosci 2014; 6: 5. [DOI:10.3389/fnsyn.2014.00005]
20. Khanabdali R, Shakouri-Motlagh A, Wilkinson S, Murthi P, Georgiou HM, Brennecke SP, et al. Low-dose aspirin treatment enhances the adhesion of preeclamptic decidual mesenchymal stem/stromal cells and reduces their production of pro-inflammatory cytokines. J Mol Med 2018; 96: 1215-25. [DOI:10.1007/s00109-018-1695-9]
21. Li Q, Zhai Y, Luo W, Zhu Z, Zhang X, Xie S, et al. Synthesis and biological properties of polyamine modified flavonoids as hepatocellular carcinoma inhibitors. Eur J Med Chem 2016; 121: 110-9. [DOI:10.1016/j.ejmech.2016.04.031]
22. Li X, Li F, Ling L, Li C, Zhong Y. Intranasal administration of nerve growth factor promotes angiogenesis via activation of pi3k/akt signaling following cerebral infarction in rats. Am J Transl Res 2018; 10: 3481.
23. Li Y, Yao D, Zhang J, Liu B, Zhang L, Feng H, et al. The effects of epidermal neural crest stem cells on local inflammation microenvironment in the defected sciatic nerve of rats. Front Mol Neurosci 2017; 10: 133. [DOI:10.3389/fnmol.2017.00133]
24. Liu Y, Chen C, Liu S, Liu D, Xu X, Chen X, et al. Acetylsalicylic acid treatment improves differentiation and immunomodulation of shed. J Dent Res 2015; 94: 209-18. [DOI:10.1177/0022034514557672]
25. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative pcr and the 2− δδct method. Methods 2001; 25: 402-8. [DOI:10.1006/meth.2001.1262]
26. Mackenzie F, Ruhrberg C. Diverse roles for vegf-a in the nervous system. Development 2012; 139: 1371-80. [DOI:10.1242/dev.072348]
27. Marei HE, Hasan A, Rizzi R, Althani A, Afifi N, Cenciarelli C, et al. Potential of stem cellbased therapy for ischemic stroke. Front Neurol 2018; 9: 34. [DOI:10.3389/fneur.2018.00034]
28. Nagelschmitz J, Blunck M, Kraetzschmar J, Ludwig M, Wensing G, Hohlfeld T. Pharmacokinetics and pharmacodynamics of acetylsalicylic acid after intravenous and oral administration to healthy volunteers. Clin Pharmacol 2014; 6: 51. [DOI:10.2147/CPAA.S47895]
29. Owjfard M, Bigdeli MR, Safari A, Namavar MR. Effects of nicorandil on neurobehavioral function, bbb integrity, edema and stereological parameters of the brain in the sub-acute phase of stroke in a rat model. J Biosci 2020; 45: 1-6. [DOI:10.1007/s12038-020-0021-1]
30. Pandamooz S, Jafari A, Salehi MS, Jurek B, Ahmadiani A, Safari A, et al. Substrate stiffness affects the morphology and gene expression of epidermal neural crest stem cells in a short term culture. Biotechnol Bioeng 2020; 117: 305-17. [DOI:10.1002/bit.27208]
31. Pandamooz S, Saied M, Nabiuni M, Dargahi L, Pourghasem M. Evaluation of epidermal neural crest stem cells in organotypic spinal cord slice culture platform. Folia Biol 2016; 62: 263.
32. Pandamooz S, Salehi MS, Safari A, Azarpira N, Heravi M, Ahmadiani A, et al. Enhancing the expression of neurotrophic factors in epidermal neural crest stem cells by valproic acid: A potential candidate for combinatorial treatment. Neurosci Lett 2019; 704: 8-14. [DOI:10.1016/j.neulet.2019.03.033]
33. Pandamooz S, Salehi MS, Zibaii MI, Ahmadiani A, Nabiuni M, Dargahi L. Epidermal neural crest stem cell‐derived glia enhance neurotrophic elements in an ex vivo model of spinal cord injury. J Cell Biochem 2018; 119: 3486-96. [DOI:10.1002/jcb.26520]
34. Pournajaf S, Valian N, Shalmani LM, Khodabakhsh P, Jorjani M, Dargahi L. Fingolimod increases oligodendrocytes markers expression in epidermal neural crest stem cells. Eur J Pharmacol 2020; 885: 173502. [DOI:10.1016/j.ejphar.2020.173502]
35. Pöyhönen S, Er S, Domanskyi A, Airavaara M. Effects of neurotrophic factors in glial cells in the central nervous system: Expression and properties in neurodegeneration and injury. Front Physiol 2019; 10: 486. [DOI:10.3389/fphys.2019.00486]
36. Safari A, Badeli-Sarkala H, Namavar MR, Kargar-Abarghouei E, Anssari N, Izadi S, et al. Neuroprotective effect of dimethyl fumarate in stroke: The role of nuclear factor erythroid 2- related factor 2. Iran J Neurol 2019; 18: 108. [DOI:10.18502/ijnl.v18i3.1633]
37. Salehi MS, Borhani-Haghighi A, Pandamooz S, Safari A, Dargahi L, Dianatpour M, et al. Dimethyl fumarate up-regulates expression of major neurotrophic factors in the epidermal neural crest stem cells. Tissue Cell 2019; 56: 114-20. [DOI:10.1016/j.tice.2019.01.004]
38. Salehi MS, Pandamooz S, Safari A, Jurek B, Tamadon A, Namavar MR, et al. Epidermal neural crest stem cell transplantation as a promising therapeutic strategy for ischemic stroke. CNS Neurosci Ther 2020; 26: 670-81. [DOI:10.1111/cns.13370]
39. Sieber-Blum M, Schnell L, Grim M, Hu YF, Schneider R, Schwab ME. Characterization of epidermal neural crest stem cell (epi-ncsc) grafts in the lesioned spinal cord. Mol Cell Neurosci 2006; 32: 67-81. [DOI:10.1016/j.mcn.2006.02.003]
40. Sisakhtnezhad S, Alimoradi E, Akrami H. External factors influencing mesenchymal stem cell fate in vitro. Eur J Cell Biol 2017; 96: 13-33. [DOI:10.1016/j.ejcb.2016.11.003]
41. Shalmani LM, Valian N, Pournajaf S, Abbaszadeh F, Dargahi L, Jorjani M. Combination therapy with astaxanthin and epidermal neural crest stem cells improves motor impairments and activates mitochondrial biogenesis in a rat model of spinal cord injury. Mitochondrion 2020; 52: 125-34. [DOI:10.1016/j.mito.2020.03.002]
42. Song CG, Zhang YZ, Wu HN, Cao XL, Guo CJ, Li YQ, et al. Stem cells: A promising candidate to treat neurological disorders. Neural Regen Res 2018; 13: 1294. [DOI:10.4103/1673-5374.235085]
43. Tanaka Y, Sonoda S, Yamaza H, Murata S, Nishida K, Kyumoto-Nakamura Y, et al. Acetylsalicylic acid treatment and suppressive regulation of akt accelerate odontogenic differentiation of stem cells from the apical papilla. J Endod 2019; 45: 591-8. [DOI:10.1016/j.joen.2019.01.016]
44. Tang J, Xiong J, Wu T, Tang Z, Ding G, Zhang C, et al. Aspirin treatment improved mesenchymal stem cell immunomodulatory properties via the 15d-pgj2/pparγ/tgf-β1 pathway. Stem Cells Dev 2014; 23: 2093-103. [DOI:10.1089/scd.2014.0081]
45. Tatham MH, Cole C, Scullion P, Wilkie R, Westwood NJ, Stark LA, et al. A proteomic approach to analyze the aspirin-mediated lysine acetylome. Mol Cell Proteomics 2017; 16: 310-26. [DOI:10.1074/mcp.O116.065219]
46. Wang Y, He G, Tang H, Shi Y, Zhu M, Kang X, et al. Aspirin promotes tenogenic differentiation of tendon stem cells and facilitates tendinopathy healing through regulating the gdf7/smad1/5 signaling pathway. J Cell Physiol 2020; 235: 4778-89. [DOI:10.1002/jcp.29355]
47. Wang Y, Tang H, He G, Shi Y, Kang X, Lyu J, et al. High concentration of aspirin induces apoptosis in rat tendon stem cells via inhibition of the wnt/β-catenin pathway. Cell Physiol Biochem 2018; 50: 2046-59. [DOI:10.1159/000495050]
48. Xiao N, Le QT. Neurotrophic factors and their potential applications in tissue regeneration. Arch Immunol Ther Exp 2016; 64: 89-99. [DOI:10.1007/s00005-015-0376-4]
49. Yuan M, Zhan Y, Hu W, Li Y, Xie X, Miao N, et al. Aspirin promotes osteogenic differentiation of human dental pulp stem cells. Int J Mol Med 2018; 42: 1967-76. [DOI:10.3892/ijmm.2018.3801]
50. Zhang H, Lu J, Jiao Y, Chen Q, Li M, Wang Z, et al. Aspirin inhibits natural killer/t-cell lymphoma by modulation of vegf expression and mitochondrial function. Front Oncol 2019; 8: 679. [DOI:10.3389/fonc.2018.00679]
51. Zhang Y, Ding N, Zhang T, Sun Q, Han B, Yu T. A tetra-peg hydrogel based aspirin sustained release system exerts beneficial effects on periodontal ligament stem cells mediated bone regeneration. Front Chem 2019; 7. [DOI:10.3389/fchem.2019.00682]
Rights and permissions
Creative Commons License This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.