Cellular and molecular mechanisms of the demyelination in the central nervous system and cell therapy approaches

Home/2017, Vol. 5, No. 1/Cellular and molecular mechanisms of the demyelination in the central nervous system and cell therapy approaches

Cell and Organ Transplantology. 2017; 5(1):74-78.
DOI: 10.22494/COT.V5I1.70

Cellular and molecular mechanisms of the demyelination in the central nervous system and cell therapy approaches

Tsymbaliuk V. I., Semenova V. M., Pichkur L. D., Velychko O. N., Egorova D. М.
A. P. Romodanov State Institute of Neurosurgery NAMS Ukraine, Kyiv, Ukraine


The review summarizes the current concepts of cell-tissue and molecular features of development of demyelinating processes in the central nervous system related to multiple sclerosis and its animal model – allergic encephalomyelitis. An analysis of recently published studies of this pathology, carried out with light and electron microscopy and immunohistochemical and molecular genetic methods, is given. New methodological approaches to the study of the pathomorhological aspects of demyelinating disorders allowed receiving in-depth understanding of the etiology and mechanisms of demyelination processes in the brain and spinal cord tissues at the cellular level and identifying the ways to develop effective modern methods of pathogenetic treatment of these diseases using cell therapy.

Key words: demyelinating diseases of the CNS; experimental allergic encephalomyelitis; neural stem cells

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1. Lisyaniy NI. Immunologiya i immunoterapiya rasseyannogo skleroza [Immunology and immunotherapy of multiple sclerosis]. Kiev, 2003. 251 p. [In Russian]
2. Sospedra M, Martin R. Immunology of multiple sclerosis. Annual Review of Immunology. 2005; 23: 683-747.
3. Trapp BD, Bo L, Mo¨rk S, Chang A. Pathogenesis of tissue injury in MS lesions. J Neuroimmunol. 1999; 98: 49-56.
4. Herz J, Zipp F, Siffrin V. Neurodegeneration in autoimmune CNS inflammation. Experimental Neurology. 2010; 225: 9-17.
5. Patel J, Balabanov R. Molecular mechanisms PC of oligodendrocyte injury in multiple sclerosis and experimental autoimmune encephalomyelitis. International Journal of Molecular Sciences. 2012; 13: 10647-659.
PMid:22949885 PMCid:PMC3431883
6. Petermann F, Korn T. Cytokines and effector T cell subsets causing autoimmune CNS disease. FEBS Letters. 2011; 585: 3747-757.
7. Bogie JF, Stinissen P, Hendriks JJ. Macrophage subsets and microglia in multiple sclerosis. Acta Neuropathologica. 2014; 128: 191-213.
8. Goldmann T, Prinz M. Role of microglia in CNS autoimmunity. Clinical Developmental Immunology. 2013; Avaliable: http://dx.doi.org/10.1155/2013/208093
9. Markov DA. Demieliniziruyushchie zabolevaniya nervnoy sistemy v eksperimente i klinike [Demyelinating diseases of the nervous system in the experiment and in the clinic]. Minsk: Nauka i tekhnika, 1975. 360 p. [In Russian]
10. Trifunović D, Djedović N, Lavrnja I, et al. Cell death of spinal cord ED1+cells in a rat model of multiple sclerosis. PeerJ. 2015; Avaliable: https://doi.org/10.7717/peerj.1189
11. Correale J. The role of macroglial activation in disease progression. Multiple Sclerosis Journal. 2014; 20(10): 1288-295.
14. Gilerovich EG, Fedorova EA, Abdurasulova IN, et al. Analiz morfologicheskikh proyavleniy vospalitel’noy reaktsii v spinnom mozgu krys Vistar na eksperimental’noy modeli [Analysis of morphological manifestations of the inflammatory reaction in wistar rat spinal cord in experimental model]. Morfologiya – Morphology. 2010; 138(5): 16-20. [In Russian]
15. Pender MP, Rist MJ. Apoptosis of inflammatory cells in immune control of the nervous system: role of glia. Glia. 2001; 36(2): 137-44.
16. Kearney H, Schneider T, Yiannakas MC, et al. Spinal cord gray matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis. Journal of Neurology, Neurosurgery & Psychiatry. 2014; 86(6): 608-14.
17. Schlaeger R, Papinutto N, Panara V, et al. Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Annals of Neurology. 2014; 76: 568-80.
PMid:25087920 PMCid:PMC5316412
18. Gilmore CP, Geurts JJ, Evangelou N, et al. Spinal cord gray matter lesions in multiple sclerosis detected by post-mortem high field MR imaging. Multiple Sclerosis. 2009; 15: 180-88.
19. Derfuss T, Parikh H, Velhin S, et al. Contactin-2/TAG-1-directed autoimmunity is identified in multiple sclerosis patients and mediates gray matter pathology in animals. Proc Natl Acad Sci USA. 2009; 106(20): 8302-307.
PMid:19416878 PMCid:PMC2688870
20. Rudick RA, Trapp BD. Gray-matter injury in multiple sclerosis. N Engl J Med. 2009; 361: 1505-550.
21. Fahmy HM, Noor NA, Mohammed FF, et al. Nigella sativa as an anti-inflammatory and promising remyelinating agent in the cortex and hippocampus of experimental autoimmune encephalomyelitis-induced rats. The Journal of Basic & Applied Zoology. 2014; 67(5): 182-95.
22. Al-Izki S, Pryce G, O’Neill JK, et al. Practical guide to the induction of relapsing progressive experimental autoimmune encephalomyelitis in the Biozzi ABH mouse. Mult Scler Relat Disord. 2012; 1: 29-38.
23. Bando Y, Nomura T, Bochimoto H, et al. Abnormal morphology of myelin and axon pathology in murine models of multiple sclerosis. Neurochemistry International. 2015; 81: 16-27.
24. Ziehn MO, Avedisian AA, Tiwari-Woodruff S, et al. Hippocampal CA1 atrophy and synaptic loss during experimental autoimmune encephalomyelitis. Lab Invest. 2010; 90(5): 774-86.
PMid:20157291 PMCid:PMC3033772
25. Chumakov PV. Belok r53 i ego universal’nye funktsii v mnogokletochnom organizme [The p53 protein and its universal functions in the multicellular organism]. Uspekhi Biologicheskoi Khimii. – Advances in biochemical chemistry. 2007; 47: 52-53. [In Russian]
26. Braithwaite A, Lu X. Some p53-binding proteins that can function as arbiters of life and death. Cell death and differentiation. 2006; 13: 984-93.
27. Theotokis P, Kleopa KA, Touloumi O, et al. Connexin43 and connexin47 alterations after neural precursor cells transplantation in experimental autoimmune encephalomyelitis. Glia. 2015; 63(10): 1772-783.
28. Constantin G, Marcon S, Rossi B, et al. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells. 2009; 27: 2624-635.
29. Dai L, Lennon DP, Eaton V, et al. Human bone marrow-derived mesenchymal stem cell induce Th2 polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009; 57: 1192-209.
PMid:19191336 PMCid:PMC2706928
30. Barhum Y, Gai-Castro S, Bahat-Stromza M, et al. Intracerebroventricular transplantation of human mesenchymal stem cells induced neurotrophic factors attenuates clinical symptoms in a mouse model of multiple sclerosis. J Mol Neurosci. 2010; 41: 129-37.
31. Bai L, Lennon DP, Caplan AI, et al. Hepatocyte growth factor mediates mesenchymal stem cell-induced recovery in multiple sclerosis models. Nature Neuroscience. 2012; 15: 862-70.
PMid:22610068 PMCid:PMC3427471
32. Fedulov AS, Borisov AV, Moskovskykh YuV, et al. Autologichnaya transplantatsiya mezenkhimal’nykh stvolovykh kletok kak metod modifikatsii klinicheskogo techeniya rasseyannogo skleroza [Autologous mesenchymal stem cells transplantation as a method of modifying the clinical course of multiple sclerosis]. Nevrologiya i neyrokhirurgiya. Vostochnaya Evropa – Neurology and Neurosurgery. Eastern Europe. 2016; 4: 516-522. [In Russian]
33. Zheleznikova GF, Skripnenko NV, Ivanova GP, et al. Faktory immunopatogeneza rasseyannogo skleroza [Factors of immunopathogenesis of multiple sclerosis]. Ros immunolog zhurn. – Russian Journal of Immunology. 2015; 9(3): 261-82. [In Russian]
34. Zafranskaya MM, Nizheharodava DB, Ivanchyk HI, et al. Dinamika tsitokinov u patsientov s rasseyannym sklerozom do i posle kletochnoy terapii [Before and after cell therapy cytokines dynamics balance in multiple sclerosis patients]. Immunopatologiya, allergologiya, infektologiya – Immunopathology, allergology, infectology. 2014; 3: 82-91. [In Russian]
35. Le Blanc K, Le Blanc K, Rasmusson I, Sundberg B. Treatment of severe acute graft-versus-host disease with third party haploidentical mesenchymal stem cells. Lancet. 2004; 363: 1439-441.
36. Klose J, Schmidt N, Melms A, et al. Suppression – of experimental autoimmune encephalomyelitis by interleukin-10 transduced neural stem/progenitor cells. Journal of Neuroinflammation. 2013; 10: 117
PMid:24053338 PMCid:PMC3852052
37. Min CK, Kim BG, Park G, et al. IL-10-transduced bone marrow mesenchymal stem cells can attenuate the severity of acute graft-versus-host disease after experimental allogeneic stem cell transplantation. Bone Marrow Transplantation. 2007; 39: 637-645.
38. Finnegan A, Kaplan CD, Cao Y, et al. Collagen-induced arthritis is exacerbated in IL-10-deficient mice. Arthritis Res Ther. 2003; 5: 18-24.
39. Kim WU, Lee WK, Ryoo JW. Suppression of collagen-induced arthritis by single administration of poly (lactic-co-glycolic acid) nanoparticles entrapping type II collagen: a novel treatment strategy for induction of oral tolerance. Arthritis Rheum. 2002; 46: 1109-120.
40. Tsymbaliuk VI, Velychko OM, Pichkur OL, et al. Effects of Warton’s jelly humans mesenchymal stem cells transfected with plasmid containing il-10 gene to the behavioral response in rats with experimental allergic encephalomyelitis. Cell and Organ Transplantology. 2015; 3(2):139-143. doi: 10.22494/COT.V3I2.14.
41. Kovalchuk MV, Deryabina OG, Pichkur LD, et al. Distribution of transplanted human mesenchymal stem cells from Wharton’s Jelly in the central nervous systems of the EAE rats. Biopolymers and Cell. 2015; 31(5): 371-78.
42. Peron JP, Jazedje T, Brandão WN, et al. Human endometrial-derived mesenchymal stem cells suppress inflammation in the central nervous system of EAE mice. Stem Cell Rev. 2012; 8(3): 940-52.
43. Rafei M, Birman E, Forner K, Galipeau J. Allogeneic Mesenchymal Stem Cells for Treatment of Experimental Autoimmune Encephalomyelitis. Molecular Therapy. 2009; 17(10): 1799-803.
PMid:19602999 PMCid:PMC2835011
44. Tsymbaliuk VI, Velychko OM, Pichkur OL, et al. Effects of human Wharton’s jelly-derived mesenchymal stem cells and interleukin-10 on behavioural responses of rats with experimental allergic encephalomyelitis. Cell and Organ Transplantology. 2015; 3(1):46-51. doi: 10.22494/COT.V3I1.19

Tsymbaliuk VI, Semenova VM, Pichkur LD, Velychko ON, Egorova DМ. Cellular and molecular mechanisms of the demyelination in the central nervous system and cell therapy approaches. Cell and Organ Transplantology. 2017; 5(1):74-78. doi:10.22494/cot.v5i1.70

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