Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 2.1
5-Year Impact Factor – 2.2
Scopus CiteScore – 3.4 (CiteScore Tracker 3.7)
Index Copernicus  – 161.11; MNiSW – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

Download original text (EN)

Advances in Clinical and Experimental Medicine

2018, vol. 27, nr 7, July, p. 873–880

doi: 10.17219/acem/73720

Publication type: original article

Language: English

Download citation:

  • BIBTEX (JabRef, Mendeley)
  • RIS (Papers, Reference Manager, RefWorks, Zotero)

Anti-inflammatory and antioxidant effects of mesenchymal and hematopoietic stem cells in a rheumatoid arthritis rat model

Hanan Abdelmawgoud1,A,B,C,D,E,F, Asmaa Saleh1,A,B,C,D,E,F

1 Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt

Abstract

Background. Mesenchymal stem cells (MSCs) are of increased importance because of their capacity to counteract inflammation and suppress host immune responses.
Objectives. The aim of the study was to compare the effectiveness of MSCs and hematopoietic stem cells (HSCs) in the treatment of rheumatoid arthritis (RA).
Material and Methods. Paw swelling was assessed by measuring the thickness of the hind paws using a caliper. Cytokines – interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and IL-10 – and rheumatoid factor (RF) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Oxidative stress biomarkers – malondialdehyde (MDA) and reduced glutathione (GSH) were assessed. Nuclear factor-kappaB (NF-κB) was detected by the western blot technique. Toll-like receptor-2 (TLR-2), matrix metalloproteinase-3 (MMP-3) and cartilage oligomeric matrix protein-1 (COMP-1) gene expression were assessed by the real-time quantitative analysis. Mesenchymal stem cells were isolated from the bone marrow (BM) of rats and HSCs were isolated from human umbilical cord blood (UCB).
Results. Paw edema, RA score, RF, cytokine assay, antioxidant state, NF-κB, TLR-2, MMP3, and COMP-1 showed improvement in the group that received MSCs compared to the group that received HSCs and the group that received methotrexate.
Conclusion. Mesenchymal stem cells are very effective in reducing RA inflammation; they are superior to HSC and methotrexate treatment. Mesenchymal stem cells could become a better therapeutic opportunity for the treatment of RA.

Key words

methotrexate, rheumatoid arthritis, mesenchymal stem cells, hematopoietic stem cells

References (38)

  1. Ikari K. Genetic risk factors for rheumatoid arthritis. Nihon Rinsho. 2016;74(6):897–901.
  2. Innala L, Sjöberg C, Möller B, et al. Co-morbidity in patients with early rheumatoid arthritis – inflammation matters. Arthritis Res Ther. 2016;18:33. doi: 10.1186/s13075-016-0928-y
  3. Choy E. Understanding the dynamics: Pathways involved in the pathogenesis of rheumatoid arthritis. Rheumatology (Oxford). 2012; 51(5):3–11.
  4. Monaco C, Nanchahal J, Taylor P, et al. Anti-TNF therapy: Past, present and future. Int Immunol. 2015;27(1):55–62.
  5. Gonzalo-Gil E, Galindo-Izquierdo M. Role of transforming growth factor-beta (TGF) beta in the physiopathology of rheumatoid arthritis. Reumatol Clin. 2014;10(3):174–179.
  6. Simmonds RE, Foxwell BM. Signalling, inflammation and arthritis: NF-kappaB and its relevance to arthritis and inflammation. Rheumatology (Oxford). 2008;47(5):584–590.
  7. Huang QQ, Pope RM. Role of toll like receptors in rheumatoid arthritis. Curr Rheumatol Rep. 2009;11(5):357–364.
  8. Aref MI, Ahmed H. Cartilage oligomeric matrix protein as new marker in diagnosis of rheumatoid arthritis. Mod Chem Appl. 2015;3(2): 1000151. doi:10.4172/2329-6798.1000151
  9. Acharya C, Yik JH, Kishore A, et al. Cartilage oligomeric matrix protein and its binding partners in the cartilage extracellular matrix: Interaction, regulation and role in chondrogenesis. Matrix Biol. 2014;37:102–111.
  10. Smolen JS, Landewé R, Breedveld FC, et al. EULAR recommendations for the management of rheumatoid arthritis with synthetic and biological disease-modifying antirheumatic drugs: 2013 update. Ann Rheum Dis. 2014;73(3):492–509.
  11. Singh JA, Saag KG, Bridges SL, et al. 2015 American College of Rheumatology Guideline for the Treatment of Rheumatoid Arthritis. Arthritis Care Res (Hoboken). 2016;68(1):1–25.
  12. Malgieri A, Kantzari E, Patrizi MP, et al. Bone marrow and umbilical cord blood human mesenchymal stem cells: State of the art [published online ahead of print September 7, 2010]. Int J Clin Exp Med. 2010;3(4):248–269.
  13. Sun L, Akiyama K, Zhang H, et al. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells. 2009;27:1421–1432.
  14. Zippel N, Limbach CA, Ratajski N, et al. Purinergic receptors influence the differentiation of human mesenchymal stem cells. Stem Cells Dev. 2012;21(6):884–900.
  15. Salem HK, Thiemermann C. Mesenchymal stromal cells: Current understanding and clinical status. Stem Cells. 2010;28(3):585–596.
  16. Saeed H, Ahsan M, Saleem Z, et al. Mesenchymal stem cells (MSCs) as skeletal therapeutics – an update [published online ahead of print April 16, 2016]. J Biomed Sci. 2016;23:41. doi: 10.1186/s12929-016-0254-3
  17. Borashan FA, Ilkhanipoor M, Hashemi M, et al. Investigation the effects of curcumin on serum hepatic enzymes activity in a rheumatoid arthritis model. eJBio. 2008;4(4):129–133.
  18. Banji D, Pinnapureddy J, Banji OJ, et al. Synergistic activity of curcumin with methotrexate in ameliorating Freund’s complete adjuvant-induced arthritis with reduced hepatotoxicity in experimental animals. Eur J Pharmacol. 2011;668(1–2):293–298.
  19. Djouad F, Bony C, Haupl T, et al. Transcriptional profiles discriminate bone marrow-derived and synovium-derived mesenchymal stem cells. Arthritis Res Ther. 2005;7:1304–1315. doi: org/10.1186/ar1827
  20. Zhao DC, Lei JX, Chen R, et al. Bone marrow derived mesenchymal stem cells protect against experimental liver fibrosis in rats. World J Gastroentrol. 2005;11(22):3431–3440.
  21. Mohamed AO, Idriss NK, Sabry D, et al. Comparative study between the effects of human CD34 and rat bone marrow mesenchymal stem cells on amelioration of CCl4 induced liver fibrosis. EJB. 2015;33(1–2):34–51.
  22. Wills ED. Evaluation of lipid peroxidation in lipids and biological membranes. In: Snell K, Mullock B, eds. Biochemical Toxicology: A practical approach. Oxford & Washington, DC: IRL Press; 1987:127–152.
  23. Ellman GL. Tissue sulfhydryl groups. Arch of Bioch & Biophys. 1959;82: 70–77.
  24. Zhao Q, Ren H, Han Z. Mesenchymal stem cells: Immunomodulatory capability and clinical potential in immune diseases. Journal of Cellular Immunotherapy. 2016;2(1):3–20.
  25. Han Z, Jing Y, Zhang S, et al. The role of immunosuppression of mesenchymal stem cells in tissue repair and tumor growth. Cell Biosci. 2012;2(1):8. doi: 10.1186/2045-3701-2-8
  26. Roberts CA, Dickinson AK, Taams LS. The interplay between monocytes/macrophages and CD4+ T cell subsets in rheumatoid arthritis. Front Immunol. 2015;6:571. doi: 10.3389/fimmu.2015.00571
  27. Park KH, Mun CH, Kang MI, et al. Treatment of collagen-induced arthritis using immune modulatory properties of human mesenchymal stem cells. Cell Transplant. 2016;25(6):1057–1072.
  28. Ganesan K, Tiwari M, Balachandran C, et al. Estrogen and testosterone attenuate extracellular matrix loss in collagen-induced arthritis in rats. Calcif Tissue Int. 2008;83(5):354–364.
  29. Augello A, Tasso R, Negrini SM, et al. Cell therapy using allogeneic bone marrow mesenchymal stem cells prevents tissue damage in collagen-induced arthritis. Arthritis Rheum. 2007;56(4):1175–1186.
  30. Liu Y, Mu R, Wang S, et al. Therapeutic potential of human umbilical cord mesenchymal stem cells in the treatment of rheumatoid arthritis. Arthritis Res Ther. 2010;12(6):210. doi: 10.1186/ar3187
  31. Mao F, Xu WR, Qian H, et al. Immunosuppressive effects of mesenchymal stem cells in collagen-induced mouse arthritis. Inflamm Res. 2010;59(3):219–225.
  32. Ren G, Zhang L, Zhao X, et al. Mesenchymal stem cell-mediated immunosuppression occurs via concerted action of chemokines and nitric oxide. Cell Stem Cell. 2008;2:141–150.
  33. Dazzi F, Krampera M. Mesenchymal stem cells and autoimmune diseases. Best Pract Res Clin Haematol. 2011;24(1):49–57.
  34. Kang MI, Park Y. Immunomodulatory function of mesenchymal stem cells for rheumatoid arthritis. J Rheum Dis. 2016;23(5):279–287.
  35. Greish S, Abogresha N, Abdel-Hady Z, et al. Human umbilical cord mesenchymal stem cells as treatment of adjuvant rheumatoid arthritis in a rat model. World J Stem Cells. 2012;4(10):101–109. doi: 10.4252/wjsc.v4.i10.101
  36. Romieu-Mourez R, Francois M, Boivin MN, et al. Cytokine modulation of TLR expression and activation in mesenchymal stromal cells leads to a proinflammatory phenotype. J Immunol. 2009;182:7963–7973.
  37. Waterman RS, Tomchuck SL, Henkle SL, et al. A new mesenchymal stem cell (MSC) paradigm: Polarization into a pro-inflammatory MSC1 or an immunosuppressive MSC2 phenotype. PLoS One. 2010;5(4): 10088. doi: 10.1371/journal.pone.0010088
  38. El-denshary ESM, Rashed LA, Elhussiny M. Mesenchymal stromal cells versus betamethasone can dampen disease activity in the collagen arthritis mouse model. Clin Exp Med. 2014;14(3):285–295.