Neuroprotective Effects of Transplanted Mesenchymal Stromal Cells-derived Human Umbilical Cord Blood Neural Progenitor Cells in EAE
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Abstract
Multiple Sclerosis (MS) is an autoimmune inflammatory demyelinating disease of the central nervous system. The aim of this study was to investigate the neuroprotective effects of transplanted human umbilical cord blood mesenchymal stromal cells (UCB-MSC) derived neural progenitor cell (MDNPC) in EAE, an experimental model of MS. To initiate neuronal differentiation of UCB-MSCs, the pre-induction medium was removed and replaced with induction media containing retinoic acid, b FGF, h EGF, NGF, IBMX and ascorbic acid for one week. The expression of neural genes was examined in comparison to control group by real-time PCR assay. Then, experimental autoimmune encephalitis (EAE) was induced using myelin oligodendrocyte glycoprotein (MOG, 35-55 peptides) in 24 C57BL/6 mice. After induction, the mice were divided in four groups (n=6) as follows: healthy, PBS, UCB-MSCs and MDNPC, respectively. At the end of the study, disease status in all the groups was analyzed using hematoxylin-eosin (H&E) staining of brain sections. We found that UCB-MSCs exhibit neuronal differentiation potential in vitro and transplanted MDNPC lowered clinical score and reduced CNS leukocyte infiltration compared to untreated mice. Our results showed that MDNPC from UCB may be a proper candidate for regenerative therapy in MS and other neurodegenerative diseases.
1. Kingwell E, Marriott JJ, Jetté N, Pringsheim T, Makhani N, Morrow SA, et al. Incidence and prevalence of multiple sclerosis in Europe: a systematic review. BMC neurol 2013; 13:128.
2. Milo R, Miller A. Revised diagnostic criteria of multiple sclerosis. Autoimmun Rev 2014; 13(4-5):518-24.
3. Minagar A, Shapshak P, Fujimura R, Ownby R, Heyes M, Eisdorfer C. The role of macrophage/microglia and astrocytes in the pathogenesis of three neurologic disorders: HIV-associated dementia, Alzheimer disease, and multiple sclerosis. J Neurol Sci 2012; 202(1-2):13-23.
4. Kim RY, Hoffman AS, Itoh N, Ao Y, Spence R, Sofroniew MV, et al. Astrocyte CCL2 sustains immune cell infiltration in chronic experimental autoimmune encephalomyelitis. J Neuroimmunol 2014; 274(1-2):53-61.
5. Steinman L, Zamvil SS. How to successfully apply animal studies in experimental allergic encephalomyelitis to research on multiple sclerosis. Ann Neurol 2006;60(1):12-21.
6. Rovaris M Confavreux C, Furlan R, Kappos L, Comi G, Filippi M. Secondary progressive multiple sclerosis: current knowledge and future challenges 2006; Lancet Neurol 2006; 5(4):343-54.
7. Knoepfler PS. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells 2009;27(5):1050-6.
8. Joyce N, Annett G, Wirthlin L, Olson S, Bauer G, Nolta JA.Mesenchymal stromal cells for the treatment of neurodegenerative disease. Regen Med 2010; 5(6):933-46.
9. Lindvall O, Kokaia Z, Martinez-Serrano A. Stem cell therapy for human neurodegenerative disorders–how to make it work 2004; (10 Suppl:S42-50).
10. Slavin S, Kurkalli BG, Karussis D. The potential use of adult stem cells for the treatment of multiple sclerosis and other neurodegenerative disorders. Clin Neurol Neurosurg 2008; 110(9):943-6.
11. Harris VK, Faroqui R, Vyshkina T, Sadiq SA.Characterization of autologous mesenchymal stem cell- derived neural progenitors as a feasible source of stem cells for central nervous system applications in multiple sclerosis. Stem Cells Transl Med 2012; 1(7):536-47.
12. Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. Clinical and pathological effects of intrathecal transplanted of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci 2012; 313(1-2):167-77.
13. Chen G, Wang Y, Xu Z, Fang F, Xu R, Wang Y, et al.Neural stem cell-like cells derived from autologous bone mesenchymal stromal cells for the treatment of patients with cerebral palsy. J Transl Med 2013; 11:21.
14. Hoveizi E, Tavakol S, Ebrahimi-Barough S.Neuroprotective Effect of Transplanted Neural Precursors Embedded on PLA/CS Scaffold in an Animal Model of Multiple Sclerosis. Mol Neurobiol 2015; 51(3):1334-42.
15. Yang J, Yan Y, Ma CG, Kang T, Zhang N, Gran B, et al.Accelerated and enhanced effect of CCR5-transduced bone marrow neural stem cells on autoimmune encephalomyelitis. Acta Neuropathol 2012; 124(4):491-503.
16. Rafieemehr H, Kheirandish M, Soleimani M. A New Two Step Induction Protocol for Neural Differentiation of Human Umbilical Cord BloodDerived Mesenchymal Stem Cells. IJBC 2015; 7(2):111-6.
17. Kögler G, Sensken S, Airey JA, Trapp T, Müschen M, Feldhahn N, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med 2004; 200(2):123-35.
18. Stromnes IM, Goverman JM. Active induction of experimental allergic encephalomyelitis. Nat Protoc 2006; 1(4):1810-9.
19. Gordon D, Pavlovska G, Glover CP, Uney JB, Wraith D, Scolding NJ. Human mesenchymal stromal cells abrogate experimental allergic encephalomyelitis after intraperitoneal transplanted, and with sparse CNS infiltration. Neurosci Lett 448(1):71-3.
20. Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, Alimoghaddom K, Talebian F, Hooshmand F, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol 2007;4(1):50-7.
21. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, et al. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol 2010;67(10):1187-94.
22. Augello A, Tasso R, Negrini SM, Cancedda R, Pennesi G. Cell therapy using allogeneic bone marrow mesenchymal stromal cells prevents tissue damage in collagen‐induced arthritis. Arthritis Rheum 2007;56(4):1175-86.
23. Higashiyama R, Inagaki Y, Hong YY, Kushida M, Nakao S, Niioka M, et al. Bone marrow–derived cells express matrix metalloproteinases and contribute to regression of liver fibrosis in mice. Hepatology 2007; 45(1):213-22.
24. Scruggs BA, Semon JA, Zhang X, Zhang S, Bowles AC, Pandey AC, et al. Age of the donor reduces the ability of human adipose-derived stem cells to alleviate symptoms in the experimental autoimmune encephalomyelitis mouse model. Stem Cells Transl Med 2013; 2(10):797-807.
25. Tisato V, Naresh K, Girdlestone J, Navarrete C, Dazzi F.Mesenchymal stromal cells of cord blood origin are effective at preventing but not treating graft-versus-host disease. Leukemia 2007; 21(9):1992-9.
26. Mojadadi, MS, Ebtekar, M, Golkar, M and Khanahmad, H. Effect of interleukin–27 on recovery from experimental autoimmune encephalomyelitis in C57BL/6 mice. KAUMS Journal (FEYZ) 2012; 16:219-28.
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| Issue | Vol 14, No 6 (2015) | |
| Section | Original Article(s) | |
| Keywords | ||
| Differentiation Experimental Autoimmune Encephalomyelitis Mesenchymal stromal cells Neural Stem Cells | ||
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