Journal of Applied Biotechnology Reports

Journal of Applied Biotechnology Reports

The Effect of Transplanted Human Wharton’s Jelly Mesenchymal Stem Cells on Matrix Metallo-proteinases in Brain of Experimental Autoimmune Encephalomyelitis Mice

Document Type : Original Article

Authors
Ali Salimi 1
Afshin Amari 2
Marzieh Ghollasi 3
Faezeh Norouz 4
1 Nanobiotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran
2 Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
3 Department of Cell and Molecular Biology, Faculty of Biological Science, Kharazmi University, Tehran, Iran
4 Department of medical nanotechnology, faculty of advanced science & technology, pharmaceutical sciences branch, Islamic azad university, Tehran, Iran
Abstract
Mesenchymal stem cells (MSCs) have immunosuppressive and anti-inflammatory properties and thus offer a potentially attractive therapeutic option for autoimmune diseases such as multiple sclerosis (MS). Matrix metalloproteinases (MMPs) are a family of extracellular enzymes that play a key role in the pathogenesis of MS. It is unclear whether MSCs affect MMPs or not. In this study, we evaluated the effect of Human Wharton’s Jelly Mesenchymal Stem Cells (hWJ-MSCs) on gene expression of MMPs in mice with experimental autoimmune encephalomyelitis (EAE). We isolated hWJ-MSCs based on explant culture. HWJ-MSCs were injected on days 3 and 11 after EAE induction. In the peak phase of disease (day 22) and 50 days after EAE induction, the brains were harvested and the expression of MMP-2, MMP-9, and tissue inhibitor of metalloproteinases-1 (TIMP-1) genes in brain of EAE mice was studied. HWJ-MSCs significantly decreased the expression of MMP-2 and MMP-9 genes but increased gene expression of TIMP-1 in brain of EAE mice. Our finding open new perspectives for understanding the mechanisms of MSCs in treatment of MS.
Keywords
Mesenchymal Stem Cells
Matrix Metalloproteinases
Experimental Autoimmune Encephalomyelitis
Metallopeptidase Inhibitor 1
  1. Sospedra, M., Martin, R., Immunology of multiple sclerosis. Annu Rev Immunol, 2005, Vol. 23, pp. 683-747.
  2. Steinman, L., Multiple sclerosis: a two-stage disease. Nature Immunol, 2001, Vol. 2, pp. 762-764.
  3. Maeda, A., Sobel, R.A., Matrix metalloproteinases in the normal human central nervous system, microglial nodules, and multiple sclerosis lesions. J Neuropathol Exp Neurol, 1996, Vol. 55, pp. 300-309.
  4. Liuzzi, G.M., Trojano, M., Fanelli, M., Avolio, C., Fasano, A., Livrea, P.,  Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis. Mult Scler, 2002, Vol. 8, pp. 222-228.
  5. Yong, V.W., Zabad, R.K., Agrawal, S., Goncalves Dasilva, A., Metz, L.M., Elevation of matrix metalloproteinases (MMPs) in multiple sclerosis and impact of immunomodulators. J Neurol Sci, 2007, Vol. 259, pp. 79-84.
  6. Lindberg, R.L., De Groot, C.J., Montagne, L., Freitag, P., van der Valk, P., Kappos, L., The expression profile of matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) in lesions and normal appearing white matter of multiple sclerosis. Brain J Neurol, 2001, Vol. 124, pp. 1743-1753.
  7. Anthony, D.C., Ferguson, B., Matyzak, M.K., Miller, K.M., Esiri, M.M., Perry, V.H., Differential matrix metalloproteinase expression in cases of multiple sclerosis and stroke. Neuropathol Appl Neurobiol, 1997, Vol. 23, pp. 406-415.
  8. Liedtke, W., Cannella, B., Mazzaccaro, R.J., Clements, J.M., Miller, K.M., Wucherpfennig, K.W., et al., Effective treatment of models of multiple sclerosis by matrix metalloproteinase inhibitors. Ann Neurol, 1998, Vol. 44, pp. 35-46.
  9. Anthony, D.C., Miller, K.M., Fearn, S., Townsend, M.J., Opdenakker, G., Wells, G.M., et al., Matrix metalloproteinase expression in an experimentally-induced DTH model of multiple sclerosis in the rat CNS.  J Neuroimmunol, 1998, Vol. 87, pp. 62-72.
  10. Leppert, D., Ford, J., Stabler, G., Grygar, C., Lienert, C., Huber, S., et al., Matrix metalloproteinase-9 (gelatinase B) is selectively elevated in CSF during relapses and stable phases of multiple sclerosis. Brain J Neurol, 1998, Vol. 121 ( Pt 12), pp. 2327-2334.
  11. Buhler, L.A., Samara, R., Guzman, E., Wilson, C.L., Krizanac-Bengez, L., Janigro, D., Matrix metalloproteinase-7 facilitates immune access to the CNS in experimental autoimmune encephalomyelitis. BMC Neurosci, 2009, Vol. 10, pp. 17-22.
  12. Cossins, J.A., Clements, J.M., Ford, J., Miller, K.M., Pigott, R., Vos, W., et al., Enhanced expression of MMP-7 and MMP-9 in demyelinating multiple sclerosis lesions. Acta Neuropathol, 1997, Vol. 94, pp. 590-598.
  13. Kieseier, B.C., Kiefer, R., Clements, J.M., Miller, K., Wells, G.M., Schweitzer, T., et al., Matrix metalloproteinase-9 and -7 are regulated in experimental autoimmune encephalomyelitis. Brain : a journal of neurology, 1998, Vol. 121 ( Pt 1), pp. 159-66.
  14. Goncalves DaSilva, A., Yong, V.W., Matrix metalloproteinase-12 deficiency worsens relapsing-remitting experimental autoimmune encephalomyelitis in association with cytokine and chemokine dysregulation. Am J Pathol, 2009, Vol. 174, pp. 898-909.
  15. Gold, S.M., Sasidhar, M.V., Morales, L.B., Du, S., Sicotte, N.L., Tiwari-Woodruff, S.K., Estrogen treatment decreases matrix metalloproteinase (MMP)-9 in autoimmune demyelinating disease through estrogen receptor alpha (ERalpha). Lab Invest, 2009, Vol. 89, pp. 1076-83.
  16. Dominici, M., Le Blanc, K., Mueller, I., Slaper-Cortenbach, I., Marini, F., Krause, D., et al., Minimal criteria for defining multipotent mesenchymal stromal cells. Int Soc Cell Ther Pos Stat Cytother, 2006, Vol. 8, pp. 315-317.
  17. Rasmusson, I., Ringden, O., Sundberg, B., Le Blanc, K., Mesenchymal stem cells inhibit the formation of cytotoxic T lymphocytes, but not activated cytotoxic T lymphocytes or natural killer cells. Transpl, 2003, Vol. 76, pp. 1208-1213.
  18. Zappia, E., Casazza, S., Pedemonte, E., Benvenuto, F., Bonanni, I., Gerdoni, E., Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood, 2005, Vol. 106, pp. 1755-1761.
  19. Aggarwal, S., Pittenger, M.F., Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood, 2005, Vol. 105, pp. 1815-1822.
  20. Kong, Q.F., Sun, B., Bai, S.S., Zhai, D.X., Wang, G.Y., Liu, Y.M., Administration of bone marrow stromal cells ameliorates experimental autoimmune myasthenia gravis by altering the balance of Th1/Th2/Th17/Treg cell subsets through the secretion of TGF-beta. J Nneuroimmunol, 2009, Vol. 207, pp. 83-91.
  21. Jiang, X.X., Zhang, Y., Liu, B., Zhang, S.X., Wu, Y., Yu, X.D., et al., Human mesenchymal stem cells inhibit differentiation and function of monocyte-derived dendritic cells. Blood, 2005, Vol. 105, pp. 4120-4126.
  22. Ramasamy, R., Fazekasova, H., Lam, E.W., Soeiro, I., Lombardi, G., Dazzi, F., Mesenchymal stem cells inhibit dendritic cell differentiation and function by preventing entry into the cell cycle. Transpl, 2007, Vol. 83, pp. 71-76.
  23. Amari, A., Ebtekar, M., Moazzeni, S.M., Soleimani, M., Mohammadi Amirabad, L., Tahoori, M.T., et al., In Vitro Generation of IL-35-expressing Human Wharton's Jelly-derived Mesenchymal Stem Cells Using Lentiviral Vector. Iran J allergy, asthma Immunol, 2015, Vol. 14, pp. 416-426.
  24. Amari, A., Ebtekar, M., Moazzeni, S.M., Soleimani, M., Amirabad, L.M., Tahoori, M.T., et al., Investigation of immunomodulatory properties of human Wharton's Jelly-derived mesenchymal stem cells after lentiviral transduction. Cell Immunol, 2015, Vol. 293, pp. 59-66.
  25. Torkaman, M., Ghollasi, M., Mohammadnia-Afrouzi, M., Salimi, A., Amari, A., The effect of transplanted human Wharton's jelly mesenchymal stem cells treated with IFN-gamma on experimental autoimmune encephalomyelitis mice. Cell Immunol, 2017, Vol. 311, pp. 1-12.
  26. Mohammadzadeh, A., Pourfathollah, A.A., Shahrokhi, S., Fallah, A., Tahoori, M.T., Amari, A., Evaluation of AD-MSC (adipose-derived mesenchymal stem cells) as a vehicle for IFN-beta delivery in experimental autoimmune encephalomyelitis. Clin Immunol, 2016, Vol. 169, pp. 98-106.
  27. Tse, W.T., Pendleton, J.D., Beyer, W.M., Egalka, M.C., Guinan, E.C., Suppression of allogeneic T-cell proliferation by human marrow stromal cells: implications in transplantation. Transpl, 2003, Vol. 75, pp. 389-397.
  28. Ryan, J.M., Barry, F.P., Murphy, J.M., Mahon, B.P., Mesenchymal stem cells avoid allogeneic rejection. J Inflam, 2005, Vol. 2, pp. 8-12.
  29. Klyushnenkova, E., Mosca, J.D., Zernetkina, V., Majumdar, M.K., Beggs, K.J., Simonetti, D.W., et al., T cell responses to allogeneic human mesenchymal stem cells: immunogenicity, tolerance, and suppression. J Biomed Sci, 2005, Vol. 12, pp. 47-57.
  30. Asari, S., Itakura, S., Ferreri, K., Liu, C.P., Kuroda, Y., Kandeel, F., et al., Mesenchymal stem cells suppress B-cell terminal differentiation. Exp Hematol, 2009, Vol. 37, pp. 604-615.
  31. Spaggiari, G.M., Capobianco, A., Abdelrazik, H., Becchetti, F., Mingari, M.C., Moretta, L., Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2. Blood, 2008, Vol. 111, pp. 1327-1333.
  32. Shimizu, F., Kanda, T., Disruption of the blood-brain barrier in inflammatory neurological diseases. Brain Nerve, 2013, Vol. 65, pp. 165-176.
  33. Van Horssen, J., Vos, C.M., Admiraal, L., van Haastert, E.S., Montagne, L., van der Valk, P., et al., Matrix metalloproteinase-19 is highly expressed in active multiple sclerosis lesions. Neuropathol Appl Neurobiol, 2006, Vol. 32, pp. 585-593.
  34. Yong, V.W., Agrawal, S.M., Stirling, D.P., Targeting MMPs in acute and chronic neurological conditions. Neurotherapeutics, 2007, Vol. 4, pp. 580-589.
  35. Yong, V.W., Power, C., Forsyth, P., Edwards, D.R., Metalloproteinases in biology and pathology of the nervous system. Nature Rev Neurosci, 2001, Vol. 2, pp. 502-511.
  36. Waubant, E., Goodkin, D., Bostrom, A., Bacchetti, P., Hietpas, J., Lindberg, R., et al., IFNbeta lowers MMP-9/TIMP-1 ratio, which predicts new enhancing lesions in patients with SPMS. Neurol, 2003, Vol. 60, pp. 52-57.
  37. Leppert, D., Lindberg, R.L., Kappos, L., Leib, S.L., Matrix metalloproteinases: multifunctional effectors of inflammation in multiple sclerosis and bacterial meningitis. Brain Res, 2001, Vol. 36, pp. 249-257.
Journal of Applied Biotechnology Reports
Volume 4, Issue 1
Winter 2017
Pages 553-557

  • Receive Date 11 February 2017
  • Accept Date 11 March 2017