Issue

Vol. 64 No. 1: Issue 1

The undersigned hereby assign all rights, included but not limited to copyright, for this manuscript to CMB Association upon its submission for consideration to publication on Cellular and Molecular Biology. The rights assigned include, but are not limited to, the sole and exclusive rights to license, sell, subsequently assign, derive, distribute, display and reproduce this manuscript, in whole or in part, in any format, electronic or otherwise, including those in existence at the time this agreement was signed. The authors hereby warrant that they have not granted or assigned, and shall not grant or assign, the aforementioned rights to any other person, firm, organization, or other entity. All rights are automatically restored to authors if this manuscript is not accepted for publication.

Long term treatment by mesenchymal stem cells conditioned medium modulates cellular, molecular and behavioral aspects of adjuvant-induced arthritis

https://doi.org/10.14715/cmb/2018.64.2.5
Vida Nazemian
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Homa Manaheji
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Ali Mohammad Sharifi
Tissue Engineering Group, Department of Orthopedic Surgery, Faculty of Medicine, University of Malaya, Kualalampur, Malaysia
Jalal Zaringhalam
Neurophysiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Corresponding Author(s) : Jalal Zaringhalam

jzaringhalam@yahoo.com

Cellular and Molecular Biology, Vol. 64 No. 1: Issue 1

Abstract

Neuroinflammation plays a crucial role in expression of symptoms of numerous autoimmune and neurodegenerative diseases such as pain during rheumatoid arthritis. Overproduction of pro-inflammatory cytokines and activation of intracellular signaling pathways have been strongly implicated in the generation of pathological pain states, particularly at central nervous system sites and induction of spinal neuroinflammatory symptoms. The wide ranges of research to define new therapeutic approaches, including neuroimmune-modulators like stem cells are in progress. Mesenchymal stem cells conditioned medium (MSC-CM) has anti-inflammatory factors which can regulate the immune responses. The aim of this study was to investigate the effect of administration of MSC-CM on behavioral, cellular and molecular aspects of adjuvant-induced arthritis in male Wistar rats. Complete Freund's adjuvant (CFA)-induced arthritis (AA) was caused by single subcutaneous injection of CFA into the rat's hind paw on day 0. MSC-CM was administered daily (i.p.) and during the 21 days of the study after injection. Hyperalgesia, Edema, Serum TNF-α levels and p38MAPK and NF-κB activities were assessed on days 0,7,14 and 21 of the study. The results of this study indicated the role of MSC-CM in reducing inflammatory symptoms, serum TNF-α levels and activity of intracellular signaling pathway factors during different phases of inflammation caused by CFA. It seems that MSC-CM treatment due to its direct effects on inhibition of intracellular signaling pathways and pro-inflammatory cytokines can alleviate inflammatory symptoms and pain during CFA-induced arthritis.

Keywords

Neuroinflammation Rheumatoid arthritis MSC-CM Hyperalgesia Edema TNF-α P38MAPK NF-κB.
Nazemian, V., Manaheji, H., Sharifi, A. M., & Zaringhalam, J. (2018). Long term treatment by mesenchymal stem cells conditioned medium modulates cellular, molecular and behavioral aspects of adjuvant-induced arthritis. Cellular and Molecular Biology, 64(1), 19–26. https://doi.org/10.14715/cmb/2018.64.2.5
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. Felderhoff-Mueser U, Schmidt OI, Oberholzer A, Bührer C, Stahel PF. IL-18: a key player in neuroinflammation and neurodegeneration? Trends Neurosci, 2005; 28:487-93.
  2. Loram LC, Taylor FR, Strand KA, Frank MG, Sholar P, Harrison JA, et al. Prior exposure to glucocorticoids potentiates lipopolysaccharide induced mechanical allodynia and spinal neuroinflammation. Brain Behav Immun, 2011; 25:1408-15.
  3. Shadnoush M, Nazemian V, Manaheji H, Zaringhalam J. Effect of probiotic administration on acute inflammatory pain. Middle East J Rehabil Health, 2017; 4:e42022.
  4. Zaringhalam J, Manaheji H, Mghsoodi N, Farokhi B, Mirzaiee V. spinal µ"opioid receptor expression and hyperalgesia with dexamethasone in chronic adjuvant"induced arthritis in rats. Clin Exp Pharmacol Physiol Suppl, 2008; 35:1309-15.
  5. Giasuddin A, Hoque M, Ahmed Z. Tumour necrosis factor-alpha as a new therapeutic target for rheumatoid arthritis: an update. Bangladesh Med Res Counc Bull, 2005; 31:88-94.
  6. Zaringhalam J, Tekieh E, Manaheji H, Akhtari Z. Cellular events during arthritis-induced hyperalgesia are mediated by Interleukin-6 and p38MAPK and their effects on the expression of spinal mu-opioid receptors. Rheumatol Int, 2013; 33:2291-99.
  7. Shih RH, Wang CY, Yang CM. NF-kappaB signaling pathways in neurological inflammation: a mini review. Front Mol Neurosci, 2015; 18:1-8.
  8. Olajide OA, Bhatia HS, de Oliveira ACP, Wright CW, Fiebich BL. Anti-neuroinflammatory properties of synthetic cryptolepine in human neuroblastoma cells: Possible involvement of NF-kB and p38MAPK inhibition. Eur J Med Chem, 2013; 63:333-9.
  9. Maumus M, Jorgensen C, Noí«l D. Mesenchymal stem cells in regenerative medicine applied to rheumatic diseases: role of secretome and exosomes. Biochimie, 2013; 95:2229-34.
  10. Platas J, Guillén MI, Pérez del Caz MD, Gomar F, Mirabet V, Alcaraz MJ. Conditioned media from adipose-tissue-derived mesenchymal stem cells downregulate degradative mediators induced by interleukin-1β in osteoarthritic chondrocytes. Mediators Inflamm, 2013; 2013:1-10.
  11. Ivanova-Todorova E, Bochev I, Dimitrov R, Belemezova K, Mourdjeva M, Kyurkchiev S, et al. Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4, FOXP3+ cells and increases IL-10 secretion. Biomed Res Int, 2012; 2012:1-8.
  12. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain, 1983; 16:109-10.
  13. Akhtari Z, Zaringhalam J, Rohani AH, Tekieh E. Role of increasing serum tumor necrosis factor on hyperalgesia and edema variation during different stages of adjuvant-induced arthritis in male rats. Koomesh, 2013; 14:357-66.
  14. Nasseri B, Nazemian V, Manaheji H, Zaringhalam J. Microglia are Involved in Pain Related Behaviors during the Acute and Chronic Phases of Arthritis Inflammation. J Cell Mol Anesth, 2016; 1:137-45.
  15. Zaringhalam J, Akbari A, Zali A, Manaheji H, Nazemian V, Shadnoush M, et al. Long-term treatment by vitamin B1 and reduction of serum proinflammatory cytokines, hyperalgesia, and paw edema in adjuvant-induced arthritis. Basic Clin Neurosci, 2016; 7:331-40.
  16. Aali E, Mirzamohammadi S, Ghaznavi H, Madjd Z, Larijani B, Rayegan S, et al. A comparative study of mesenchymal stem cell transplantation with its paracrine effect on control of hyperglycemia in type 1 diabetic rats. J Diabetes Metab Disord, 2014; 13:76-85.
  17. Nazemian V, Nasseri B, Manaheji H, Zaringhalam J. Effects of Mesenchymal Stem Cells Conditioned Medium on Behavioral Aspects of Inflammatory Arthritic Pain Induced by Complete Freund's Adjuvant. J Cell Mol Anesth, 2016; 1:47-55.
  18. Zhao Y, Joshi-Barve S, Barve S. Eicosapentaenoic acid prevents LPS-induced TNF-α expression by preventing NF-κB activation. J Am Coll Nutr, 2004; 23:71-8.
  19. Deleo JA, Tanga FY, Tawfik VL. Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia. Neuroscientist, 2004; 10:40-52.
  20. Inglis JJ, Nissim A, Lees DM, Hunt SP, Chernajovsky Y, kidd BL. The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation. Arthritis Res Ther, 2005; 7:807-16.
  21. Yew TL, Yeh-Ting H, Hsin-Yang L, Hsin-Wei C, Ling-Lan C, Tsai KS, et al. Enhancement of wound healing by human multipotent stromal cell conditioned medium: the paracrine factors and p38 MAPK activation. Cell Transplant, 2011; 20:693-706.
  22. Wang C, Zhang T, Liu W, Meng H, Song Y, Wang W. Sox-9 induced chondrogenesis in mesenchymal stem cells was mediated by ERK5 signal pathway. Cell Mol Biol (Noisy-le-grand), 2016; 4:1-7.
  23. Li Y-P, Niu A, Wen Y. Regulation of myogenic activation of p38 MAPK by TACE-mediated TNFα release. Front Cell Dev Biol, 2014; 2:1-5.
  24. Thalhamer T, McGrath MA, Harnett MM. MAPKs and their relevance to arthritis and inflammation. Rheumatology, 2008; 47:409-14.
  25. Christman JW, Lancaster LH, Blackwell TS. Nuclear factor k B: a pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med, 1998; 24:1131-8.
  26. Roman-Blas JA, Jimenez SA. NF-kB as a potential therapeutic target in osteoarthritis and rheumatoid arthritis. Osteoarthritis Cartilage, 2006; 14:839-48.
  27. Roshak AK, Callahan JF, Blake SM. Small-molecule inhibitors of NF-κB for the treatment of inflammatory joint disease. Curr Opin Pharmacol, 2002; 2:316-21.
  28. Han Z, Boyle DL, Manning AM, Firestein GS. AP-1 and NF-kB regulation in rheumatoid arthritis and murine collagen-induced arthritis. Autoimmunity, 1998; 28:197-208.
  29. Mbalaviele G, Monahan JB. Mechanisms of the joint-protective effects of p38MAPK inhibitors in rodent arthritis. Expert Opin Drug Discov, 2008; 3:163-72.
  30. Phull AR, Eo SH, Kim SJ. Oleanolic acid (OA) regulates inflammation and cellular dedifferentiation of chondrocytes via MAPK signaling pathways. Cell Mol Biol (Noisy-le-grand), 2017; 31:12-17.
Read More
Author biographies is not available.
Crossref
Scopus
Google Scholar
Europe PMC
Download this PDF file
PDF
Statistic
Read Counter : 1052 Download : 425