Mesenchymal Stem Cells as A New Approach for the Treatment of Multiple Sclerosis: A Literature Review
Abstract
Multiple sclerosis (MS) is a high-prevalence autoimmune and neurodegenerative disease that affects young adults. An ideal treatment for MS should have two characteristics. First, its immunosuppression and immunomodulation effects reduce the abnormal immune response, and second, it improves repair by enhancing intrinsic repair processes or even cell replacement. Most available therapies have the first characteristic. Recent studies have proposed mesenchymal stem cells (MSCs) as a new therapeutic candidate for MS. Different clinical trials and animal models of MS have shown the therapeutic effect of MSCs. In the current study, we reviewed the therapeutic effects of MSCs in the animal model and patients with MS.References
Jafarinia M, Amoon M, Javid A, Vakili S, Sadeghi E, Azadi D, et al. Male microchimerism in peripheral blood from women with multiple sclerosis in Isfahan Province. Int J Immunogenet. 2020;47(2):175-9.
https://doi.org/10.1111/iji.12465
PMid:31833227
Jafarinia M, Ashja-Arvan M, Hosseininasab F, Vakili S, Sadeghi E, Etemadifar M, et al. Evaluation of plasma soluble CD137 level in relapsing-remitting multiple sclerosis patients in comparison with healthy controls in Isfahan Province, Iran. Neurology Asia. 2020;25(3):361-5.
Browne P, Chandraratna D, Angood C, Tremlett H, Baker C, Taylor BV, et al. Atlas of multiple sclerosis 2013: a growing global problem with widespread inequity. Neurology. 2014;83(11):1022-4.
https://doi.org/10.1212/WNL.0000000000000768
PMid:25200713 PMCid:PMC4162299
Ascherio A. Environmental factors in multiple sclerosis. Expert Rev Neurother. 2013;13(sup2):3-9.
https://doi.org/10.1586/14737175.2013.865866
PMid:24289836
Jafarinia M, Sadeghi E, Alsahebfosoul F, Etemadifar M, Jahanbani-Ardakani H. Evaluation of plasma Osteopontin level in relapsing-remitting multiple sclerosis patients compared to healthy subjects in Isfahan Province. Int J Neurosci. 2020;130(5):493-8.
https://doi.org/10.1080/00207454.2019.1694925
PMid:31795798
Greenfield AL, Hauser SL. B‐cell Therapy for Multiple Sclerosis: Entering an era. Ann Neurol. 2018;83(1):13-26.
https://doi.org/10.1002/ana.25119
PMid:29244240 PMCid:PMC5876115
Leray E, Yaouanq J, Le Page E, Coustans M, Laplaud D, Oger J, et al. Evidence for a two-stage disability progression in multiple sclerosis. Brain. 2010;133(7):1900-13.
https://doi.org/10.1093/brain/awq076
PMid:20423930 PMCid:PMC2892936
Loma I, Heyman R. Multiple sclerosis: pathogenesis and treatment. Curr Neuropharmacol. 2011;9(3):409-16.
https://doi.org/10.2174/157015911796557911
PMid:22379455 PMCid:PMC3151595
Hauser SL, Cree BA. Treatment of multiple sclerosis: a review. Am J Med. 2020;133(12):1380-90.
https://doi.org/10.1016/j.amjmed.2020.05.049
PMid:32682869 PMCid:PMC7704606
Sormani MP, Muraro PA, Schiavetti I, Signori A, Laroni A, Saccardi R, et al. Autologous hematopoietic stem cell transplantation in multiple sclerosis: a meta-analysis. Neurology. 2017;88(22):2115-22.
https://doi.org/10.1212/WNL.0000000000003987
PMid:28455383
Ramagopalan SV, Dobson R, Meier UC, Giovannoni G. Multiple sclerosis: risk factors, prodromes, and potential causal pathways. The Lancet Neurology. 2010;9(7):727-39.
https://doi.org/10.1016/S1474-4422(10)70094-6
PMid:20610348
Al-Obaidi ZMJ, Hussein YA, AL-Duhaidahawi D, Al-Aubaidy HA. Molecular docking studies and biological evaluation of luteolin on cerebral ischemic reperfusion injury. Egyptian Journal of Chemistry. 2022;65(6):1-2.
Hollenbach JA, Oksenberg JR. The immunogenetics of multiple sclerosis: a comprehensive review. J Autoimmun. 2015;64:13-25.
https://doi.org/10.1016/j.jaut.2015.06.010
PMid:26142251 PMCid:PMC4687745
Kurtzke JF. Epidemiology in multiple sclerosis: a pilgrim's progress. Brain. 2013;136(9):2904-17.
https://doi.org/10.1093/brain/awt220
PMid:23983034
Pakpoor J, Disanto G, Gerber JE, Dobson R, Meier UC, Giovannoni G, et al. The risk of developing multiple sclerosis in individuals seronegative for Epstein-Barr virus: a meta-analysis. Mult Scle. 2013;19(2):162-6.
https://doi.org/10.1177/1352458512449682
PMid:22740437
Handel AE, Williamson AJ, Disanto G, Handunnetthi L, Giovannoni G, Ramagopalan SV. An updated meta-analysis of risk of multiple sclerosis following infectious mononucleosis. PLoS One. 2010;5(9):e12496.
https://doi.org/10.1371/journal.pone.0012496
PMid:20824132 PMCid:PMC2931696
Lang HL, Jacobsen H, Ikemizu S, Andersson C, Harlos K, Madsen L, et al. A functional and structural basis for TCR cross-reactivity in multiple sclerosis. Nat Immunol. 2002;3(10):940.
https://doi.org/10.1038/ni835
PMid:12244309
Tracy SI, Kakalacheva K, Lünemann JD, Luzuriaga K, Middeldorp J, Thorley-Lawson DA. Persistence of Epstein-Barr virus in self-reactive memory B cells. J Virol. 2012;86(22):12330-40.
https://doi.org/10.1128/JVI.01699-12
PMid:22951828 PMCid:PMC3486485
Koch-Henriksen N, Sørensen PS. The changing demographic pattern of multiple sclerosis epidemiology. The Lancet Neurology. 2010;9(5):520-32.
https://doi.org/10.1016/S1474-4422(10)70064-8
PMid:20398859
Palacios N, Alonso A, BrØnnum-Hansen H, Ascherio A. Smoking and increased risk of multiple sclerosis: parallel trends in the sex ratio reinforce the evidence. Ann Epidemiol. 2011;21(7):536-42.
https://doi.org/10.1016/j.annepidem.2011.03.001
PMid:21550815 PMCid:PMC3124940
Handel AE, Williamson AJ, Disanto G, Dobson R, Giovannoni G, Ramagopalan SV. Smoking and multiple sclerosis: an updated meta-analysis. PLoS One. 2011;6(1):e16149.
https://doi.org/10.1371/journal.pone.0016149
PMid:21249154 PMCid:PMC3020969
Napier MD, Poole C, Satten GA, Ashley-Koch A, Marrie RA, Williamson DM. Heavy metals, organic solvents, and multiple sclerosis: An exploratory look at gene-environment interactions. Arch Environ Occup Health. 2016;71(1):26-34.
https://doi.org/10.1080/19338244.2014.937381
PMid:25137520 PMCid:PMC4334728
Hedström AK, Bäärnhielm M, Olsson T, Alfredsson L. Tobacco smoking, but not Swedish snuff use, increases the risk of multiple sclerosis. Neurology. 2009;73(9):696-701.
https://doi.org/10.1212/WNL.0b013e3181b59c40
PMid:19720976
Orton S-M, Herrera BM, Yee IM, Valdar W, Ramagopalan SV, Sadovnick AD, et al. Sex ratio of multiple sclerosis in Canada: a longitudinal study. The Lancet Neurology. 2006;5(11):932-6.
https://doi.org/10.1016/S1474-4422(06)70581-6
PMid:17052660
Pearce J. Historical descriptions of multiple sclerosis. Eur Neurol. 2005;54(1):49-53.
https://doi.org/10.1159/000087387
https://doi.org/10.1159/000091429
Karussis D. The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun. 2014;48:134-42.
https://doi.org/10.1016/j.jaut.2014.01.022
PMid:24524923
Lassmann H. Pathology and disease mechanisms in different stages of multiple sclerosis. J Neurol Sci. 2013;333(1-2):1-4.
https://doi.org/10.1016/j.jns.2013.05.010
PMid:23735777
Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mörk S, Bö L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med. 1998;338(5):278-85.
https://doi.org/10.1056/NEJM199801293380502
PMid:9445407
Frischer JM, Bramow S, Dal-Bianco A, Lucchinetti CF, Rauschka H, Schmidbauer M, et al. The relation between inflammation and neurodegeneration in multiple sclerosis brains. Brain. 2009;132(5):1175-89.
https://doi.org/10.1093/brain/awp070
PMid:19339255 PMCid:PMC2677799
Tallantyre E, Bø L, Al-Rawashdeh O, Owens T, Polman C, Lowe J, et al. Greater loss of axons in primary progressive multiple sclerosis plaques compared to secondary progressive disease. Brain. 2009;132(5):1190-9.
https://doi.org/10.1093/brain/awp106
PMid:19420101
Mohamed Saleh Omar Korbag S, Mohamed Saleh Omar Korbag I. A new study biological role of HPV infection, oral contraceptive use, sex hormones and bisphenol A and increase rate cancer of cervical in Libya. Journal of Medicinal and Chemical Sciences. 2020;3(4):354-62.
Dobson R, Giovannoni G. Multiple sclerosis-a review. Eur Neurol. 2019;26(1):27-40.
https://doi.org/10.1111/ene.13819
PMid:30300457
Wei X, Yang X, Han Z-p, Qu F-f, Shao L, Shi Y-f. Mesenchymal stem cells: a new trend for cell therapy. Acta Pharmacol Sin. 2013;34(6):747-54.
https://doi.org/10.1038/aps.2013.50
PMid:23736003 PMCid:PMC4002895
Jafarinia M, Alsahebfosoul F, Salehi H, Eskandari N, Ganjalikhani-Hakemi M. Mesenchymal stem cell-derived extracellular vesicles: a novel cell-free therapy. Immunol Invest. 2020;49(7):758-80.
https://doi.org/10.1080/08820139.2020.1712416
PMid:32009478
Shadmanesh A, Nazari H, Shirazi A, Ahmadi E, Shams-Esfandabadi N. An inexpensive and simple method for isolation mesenchymal stem cell of human amnion membrane. International Journal of Advanced Biological and Biomedical Research. 2021;9(1):119-27.
Berebichez-Fridman R, Montero-Olvera PR. Sources and clinical applications of mesenchymal stem cells: state-of-the-art review. Sultan Qaboos Univ Med J. 2018;18(3):e264.
https://doi.org/10.18295/squmj.2018.18.03.002
PMid:30607265 PMCid:PMC6307657
Dominici M, Le Blanc K, Mueller I, Slaper-Cortenbach I, Marini F, Krause D, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The International Society for Cellular Therapy position statement. Cytotherapy. 2006;8(4):315-7.
https://doi.org/10.1080/14653240600855905
PMid:16923606
Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine. Int J Mol Sci. 2017;18(9):1852.
https://doi.org/10.3390/ijms18091852
PMid:28841158 PMCid:PMC5618501
Eleuteri S, Fierabracci A. Insights into the secretome of mesenchymal stem cells and its potential applications. Int J Mol Sci. 2019;20(18):4597.
https://doi.org/10.3390/ijms20184597
PMid:31533317 PMCid:PMC6770239
Harrell CR, Fellabaum C, Jovicic N, Djonov V, Arsenijevic N, Volarevic V. Molecular mechanisms responsible for therapeutic potential of mesenchymal stem cell-derived secretome. Cells. 2019;8(5):467.
https://doi.org/10.3390/cells8050467
PMid:31100966 PMCid:PMC6562906
Jafarinia M, Alsahebfosoul F, Salehi H, Eskandari N, Azimzadeh M, Mahmoodi M, et al. Therapeutic effects of extracellular vesicles from human adipose‐derived mesenchymal stem cells on chronic experimental autoimmune encephalomyelitis. J Cell Physiol. 2020;235(11):8779-90.
https://doi.org/10.1002/jcp.29721
PMid:32329062
Ghasemi N. Transdifferentiation of human adipose-derived mesenchymal stem cells into oligodendrocyte progenitor cells. Iran J Neurol. 2018;17(1):24.
Jadasz JJ, Tepe L, Beyer F, Samper Agrelo I, Akkermann R, Spitzhorn LS, et al. Human mesenchymal factors induce rat hippocampal‐and human neural stem cell dependent oligodendrogenesis. Glia. 2018;66(1):145-60.
https://doi.org/10.1002/glia.23233
PMid:28940767
Song N, Scholtemeijer M, Shah K. Mesenchymal stem cell immunomodulation: mechanisms and therapeutic potential. Trends Pharmacol Sci. 2020;41(9):653-64.
https://doi.org/10.1016/j.tips.2020.06.009
PMid:32709406 PMCid:PMC7751844
Jiang W, Xu J. Immune modulation by mesenchymal stem cells. Cell Proliferation. 2020;53(1):e12712.
https://doi.org/10.1111/cpr.12712
Kassis I, Grigoriadis N, Gowda-Kurkalli B, Mizrachi-Kol R, Ben-Hur T, Slavin S, et al. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol. 2008;65(6):753-61.
https://doi.org/10.1001/archneur.65.6.753
PMid:18541795
Li J, Chen Y, Chen Z, Huang Y, Yang D, Su Z, et al. Therapeutic effects of human adipose tissue-derived stem cell (hADSC) transplantation on experimental autoimmune encephalomyelitis (EAE) mice. Sci Rep. 2017;7:42695.
https://doi.org/10.1038/srep42695
PMid:28198408 PMCid:PMC5309875
Cohen JA, Imrey PB, Planchon SM, Bermel RA, Fisher E, Fox RJ, et al. Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Mult Scler. 2018;24(4):501-11.
https://doi.org/10.1177/1352458517703802
PMid:28381130 PMCid:PMC5623598
Anderson P, Gonzalez-Rey E, O'Valle F, Martin F, Oliver FJ, Delgado M. Allogeneic adipose-derived mesenchymal stromal cells ameliorate experimental autoimmune encephalomyelitis by regulating self-reactive T cell responses and dendritic cell function. Stem Cells Int. 2017;2017:2389753.
https://doi.org/10.1155/2017/2389753
PMid:28250776 PMCid:PMC5303870
Niapour N, Taghipour Z, Salehi H, Bagheri A, Rouhani A, Talebi M, et al. Isolation and identification of mesenchymal and neural crest characteristics of dental pulp derived stem cells. Koomesh. 2015;16(4):520-6.
Koc O, Lazarus H. Mesenchymal stem cells: heading into the clinic. Bone Marrow Transplant. 2001;27(3):235.
https://doi.org/10.1038/sj.bmt.1702791
PMid:11277170
Sarvar DP, Shamsasenjan K, Akbarzadehlaleh P. Mesenchymal stem cell-derived exosomes: new opportunity in cell-free therapy. Adv Pharm Bull. 2016;6(3):293.
https://doi.org/10.15171/apb.2016.041
PMid:27766213 PMCid:PMC5071792
Horwitz EM, Andreef M, Frassoni F. Mesenchymal stromal cells. Curr Opin Hematol. 2006;13(6):419.
https://doi.org/10.1097/01.moh.0000245697.54887.6f
PMid:17053453 PMCid:PMC3365862
Abdi R, Fiorina P, Adra CN, Atkinson M, Sayegh MH. Immunomodulation by mesenchymal stem cells: a potential therapeutic strategy for type 1 diabetes. Diabetes. 2008;57(7):1759-67.
https://doi.org/10.2337/db08-0180
PMid:18586907 PMCid:PMC2453631
Gallina C, Turinetto V, Giachino C. A new paradigm in cardiac regeneration: the mesenchymal stem cell secretome. Stem Cells Int. 2015;2015:1-10.
https://doi.org/10.1155/2015/765846
PMid:26074978 PMCid:PMC4436518
Bonab MM, Mohajeri M, Sahraian MA, Yazdanifar M, Aghsaie A, Farazmand A, et al. Evaluation of cytokines in multiple sclerosis patients treated with mesenchymal stem cells. Arch Med Res. 2013;44(4):266-72.
https://doi.org/10.1016/j.arcmed.2013.03.007
PMid:23684533
Yamout B, Hourani R, Salti H, Barada W, El-Hajj T, Al-Kutoubi A, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 2010;227(1-2):185-9.
https://doi.org/10.1016/j.jneuroim.2010.07.013
PMid:20728948
Sato T, Iso Y, Uyama T, Kawachi K, Wakabayashi K, Omori Y, et al. Coronary vein infusion of multipotent stromal cells from bone marrow preserves cardiac function in swine ischemic cardiomyopathy via enhanced neovascularization. Lab Invest. 2011;91(4):553.
https://doi.org/10.1038/labinvest.2010.202
PMid:21283079
Zappia E, Casazza S, Pedemonte E, Benvenuto F, Bonanni I, Gerdoni E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106(5):1755-61.
https://doi.org/10.1182/blood-2005-04-1496
PMid:15905186
Constantin G, Marconi S, Rossi B, Angiari S, Calderan L, Anghileri E, et al. Adipose‐derived mesenchymal stem cells ameliorate chronic experimental autoimmune encephalomyelitis. Stem Cells. 2009;27(10):2624-35.
https://doi.org/10.1002/stem.194
PMid:19676124
Gerdoni E, Gallo B, Casazza S, Musio S, Bonanni I, Pedemonte E, et al. Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol. 2007;61(3):219-27.
https://doi.org/10.1002/ana.21076
PMid:17387730
Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. The Lancet Neurology. 2012;11(2):150-6.
https://doi.org/10.1016/S1474-4422(11)70305-2
PMid:22236384
Stepien A, Dabrowska NL, Maciagowska M, Macoch RP, Zolocinska A, Mazur S, et al. Clinical application of autologous adipose stem cells in patients with multiple sclerosis: preliminary results. Mediators Inflamm. 2016;2016:5302120.
https://doi.org/10.1155/2016/5302120
PMid:27761060 PMCid:PMC5059576
Mohyeddin Bonab M, Ali Sahraian M, Aghsaie A, Ahmadi Karvigh S, Massoud Hosseinian S, Nikbin B, et al. Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study. Curr Stem Cell Res Ther. 2012;7(6):407-14.
https://doi.org/10.2174/157488812804484648
PMid:23061813
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.
https://doi.org/10.1001/archneurol.2010.248
PMid:20937945 PMCid:PMC3036569
Liu J, Feng B, Xu Y, Zhu J, Feng X, Chen W, et al. Immunomodulatory effect of mesenchymal stem cells in chemical-induced liver injury: a high-dimensional analysis. Stem Cell Res Ther. 2019;10(1):1-13.
https://doi.org/10.1186/s13287-019-1379-6
PMid:31443686 PMCid:PMC6708172
Herrero C, Perez-Simon J. Immunomodulatory effect of mesenchymal stem cells. Braz J Med Biol Res. 2010;43(5):425-30.
https://doi.org/10.1590/S0100-879X2010007500033
PMid:20490429

Copyright (c) 2022 Galen Medical Journal

This work is licensed under a Creative Commons Attribution 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution 4.0 International License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).