The survival of transplanted mesenchymal stem cells from humans Wharton’s jelly of the umbilical cord in the central nervous system of rats with experimental allergic encephalomyelitis after their suboccipital injection

Leonid D. Pichkur, Mariia V. Кovalchuk, Olena G. Deriabina, Svitlana A. Verbovska, Samuel T. Akinola, Nadiia S. Shuvalova, Vitalii А. Коrdium

Abstract


Human Wharton’s Jelly of mesenchymal stem cells (hWJ-MSCs) have a considerable advantage in comparison with the cells from other sources; their therapeutic potential in treating the central nervous system (CNS) diseases is higher than that of other MSCs. That’s why hWJ-MSCs can be a new alternative treatment of CNS demyelinization damages including multiple sclerosis (MS).

Purpose. To study the persistence and distribution of hWJ-MSCs in different CNS segments following suboccipital transplantation into cerebrospinal fluid (CSF) of rats with experimental allergic encephalomyelitis (EAE).

Methods. Isolation and cultivation of hWJ-MSCs in vitro. Immunological phenotyping by flow cytometry. EAE induction. Suboccipital injection of MSCs into EAE rats cerebrospinal fluid. Persistence of hWJ-MSCs in the CNS of EAE rats was assayed by PCR in tissue samples at days 2, 3, 4 and 5 using primers for amplifying nucleic alpha satellite sequences of human 17th chromosome.

Results. PCR-assays for alpha-satellite sequences revealed human DNA to be detected in the treated rats within 5 days after suboccipital injection at the peak of disease. The human DNA was traced in CSF and various segments of the spinal cord.

Conclusions. The data obtained suggest that suboccipitally delivered hWJ-MSCs, survive and can migrate through the CSF from the injection site (cisterna magna) to various segments of CNS. 


Keywords


experimental allergic encephalomyelitis; mesenchymal stem cells from humans Wharton’s jelly of umbilical cord; demyelinization damages; PCR-analysis

References


1. Darlington PJ, Boivin MN, Bar-Or A. Harnessing the therapeutic potential of mesenchymal stem cells in multiple sclerosis. Expert Rev Neurother. 2011 Sep;11(9):1295-303. [CrossRef] [PubMed] [PubMed Central]

2. Hшglund RA, Maghazachi AA. Multiple sclerosis and the role of immune cells. World J Exp Med. 2014 Aug 20;4(3):27-37. [CrossRef] [PubMed] [PubMed Central]

3. Mastorodemos V, Ioannou M, Verginis P. Cell-based modulation of autoimmune responses in multiple sclerosis and experimental autoimmmune encephalomyelitis: therapeutic implications. Neuroimmunomodulation. 2015;22(3):181-95. [CrossRef] [PubMed]

4. Goldenberg MM. Multiple sclerosis review. P T. 2012 Mar;37(3):175-84. [PubMed] [PubMed Central]

5. Karussis D, Karageorgiou C, Vaknin-Dembinsky A, Gowda-Kurkalli B, Gomori JM, Kassis I, Bulte JW, Petrou P, Ben-Hur T, Abramsky O, Slavin S. Safety and immunological effects of mesenchymal stem cell transplantation in patients with multiple sclerosis and amyotrophic lateral sclerosis. Arch Neurol. 2010 Oct;67(10):1187-94. [CrossRef] [PubMed] [PubMed Central]

6. Cohen JA. Mesenchymal stem cell transplantation in multiple sclerosis. J Neurol Sci. 2013 Oct 15;333(1-2):43-9. [CrossRef] [PubMed] [PubMed Central]

7. Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, Gini B, Bach SD, Martinello M, Bifari F, Galiи M, Turano E, Budui S, Sbarbati A, Krampera M, Bonetti B. Adipose-derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells. 2009 Oct;27(10):2624-35. [CrossRef] [PubMed]

8. Axelsson M, Malmestrцm C, Gunnarsson M, Zetterberg H, Sundstrцm P, Lycke J, Svenningsson A. Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis. Mult Scler. 2014 Jan;20(1):43-50. [CrossRef] [PubMed]

9. Lublin FD, Bowen JD, Huddlestone J, Kremenchutzky M, Carpenter A, Corboy JR, Freedman MS, Krupp L, Paulo C, Hariri RJ, Fischkoff SA. Human placenta-derived cells (PDA-001) for the treatment of adults with multiple sclerosis: a randomized, placebo-controlled, multiple-dose study. Mult Scler Relat Disord. 2014 Nov;3(6):696-704. [CrossRef] [PubMed]

10. Uccelli A, Laroni A, Freedman MS. Mesenchymal stem cells for the treatment of multiple sclerosis and other neurological diseases. Lancet Neurol. 2011 Jul;10(7):649-56. [CrossRef] [PubMed]

11. Keating A. Mesenchymal stromal cells: new directions. Cell Stem Cell. 2012 Jun 14;10(6):709-16. [CrossRef] [PubMed]

12. Nakano N, Nakai Y, Seo TB, Homma T, Yamada Y, Ohta M, Suzuki Y, Nakatani T, Fukushima M, Hayashibe M, Ide C. Effects of bone marrow stromal cell transplantation through CSF on the subacute and chronic spinal cord injury in rats. PLoS One. 2013 Sep 11;8(9):e73494. [CrossRef] [PubMed] [PubMed Central]

13. Isakova IA, Baker K, DuTreil M, Dufour J, Gaupp D, Phinney DG. Age- and dose-related effects on MSC engraftment levels and anatomical distribution in the central nervous systems of nonhuman primates: identification of novel MSC subpopulations that respond to guidance cues in brain. Stem Cells. 2007 Dec;25(12):3261-70. [CrossRef] [PubMed]

14. Phinney DG, Baddoo M, Dutreil M, Gaupp D, Lai WT, Isakova IA. Murine mesenchymal stem cells transplanted to the central nervous system of neonatal versus adult mice exhibit distinct engraftment kinetics and express receptors that guide neuronal cell migration. Stem Cells Dev. 2006 Jun;15(3):437-47. [CrossRef] [PubMed]

15. Zhao G, Liu F, Lan S, Li P, Wang L, Kou J, Qi X, Fan R, Hao D, Wu C, Bai T, Li Y, Liu JY. Large-scale expansion of Wharton's jelly-derived mesenchymal stem cells on gelatin microbeads, with retention of self-renewal and multipotency characteristics and the capacity for enhancing skin wound healing. Stem Cell Res Ther. 2015 Mar 19;6:38. [CrossRef] [PubMed] [PubMed Central]

16. Romo-Gonzбlez T, Chavarrнa A, Pйrez-H J. Central nervous system: a modified immune surveillance circuit? Brain Behav Immun. 2012 Aug;26(6):823-9. [CrossRef] [PubMed]

17. [Law of Ukraine No 3447-IV On the Protection of Animals from Cruelty] [Internet]. Verkhovna Rada of Ukraine. 2017 [cited 24 May 2017]. Ukrainian. Available from: http://zakon2.rada.gov.ua/laws/show/3447-15.

18. European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes [Internet]. Council of Europe. 2017 [cited 24 May 2017]. Available from: https://rm.coe.int/168007a67b.

19. Maslova OO, Shuvalova NS, Sukhorada OM, Zhukova SM, Deryabina OG, Makarenko MV, et al. Heterogeneity of Umbilical Cords as a Source for Mesenchymal Stem Cells. Dataset Papers in Biology. Hindawi Limited; 2013;2013:1–4. [CrossRef]

20. Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, Deans R, Keating A, Prockop Dj, Horwitz E. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7. [CrossRef] [PubMed]

21. Feurer C,PrenticeDE, Cammisuli S. Chronic relapsing experimental allergic encephalomyelitis in the Lewis rat. J Neuroimmunol. 1985 Dec;10(2):159-66. [CrossRef] [PubMed]

22. Miller SD, Karpus WJ, Davidson TS. Experimental autoimmune encephalomyelitis in the mouse. Curr Protoc Immunol. 2010 Feb;Chapter 15:Unit 15.1. [CrossRef] [PubMed]

23. Grimberg J, Nawoschik S, Belluscio L, McKee R, Turck A, Eisenberg A. A simple and efficient non-organic procedure for the isolation of genomic DNA from blood. Nucleic Acids Res. 1989 Oct 25;17(20):8390. [CrossRef] [PubMed] [PubMed Central]

24. Biase FH, Franco MM, Goulart LR, Antunes RC. Protocol for extraction of genomic DNA from swine solid tissues. Genet Mol Biol. 2002;25(3):313–315. [CrossRef]

25. Becker M, Nitsche A, Neumann C, Aumann J, Junghahn I, Fichtner I. Sensitive PCR method for the detection and real-time quantification of human cells in xenotransplantation systems. Br J Cancer. 2002 Nov 18;87(11):1328-35. [CrossRef] [PubMed] [PubMed Central]

26. Kovalchuk MV, Shuvalova NS, Pokholenko IO, Draguljan MV, Gulko TP, Deryabina OG, Kordium VA. Monitoring of transplanted human mesenchymal stem cells from Wharton’s jelly in xenogeneic systems in vivo. Biopolymers and Cells. 2015;31(3):193-199. [CrossRef]


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DOI: https://doi.org/10.25305/unj.112102

Copyright (c) 2017 Leonid D. Pichkur, Mariia V. Кovalchuk, Olena G. Deriabina, Svitlana A. Verbovska, Samuel T. Akinola, Nadiia S. Shuvalova, Vitalii А. Коrdium

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