Opportunities and challenges: mesenchymal stem cells in the treatment of multiple sclerosis

References

• Compston A, Coles A. Multiple sclerosis. Lancet. 2008;372(9648):1502–1517.
   PubMed Web of Science ®Google Scholar
• Brownlee WJ, Hardy TA, Fazekas F, et al. Diagnosis of multiple sclerosis: progress and challenges. Lancet. 2017;389(10076):1336–1346.
   PubMed Web of Science ®Google Scholar
• Rivera FJ, Aigner L. Adult mesenchymal stem cell therapy for myelin repair in multiple sclerosis. Biol Res. 2012;45(3):257–268.
   PubMed Web of Science ®Google Scholar
• Jadasz JJ, Aigner L, Rivera FJ, et al. The remyelination philosopher’s stone: stem and progenitor cell therapies for multiple sclerosis. Cell Tissue Res. 2012;349(1):331–347.
   PubMed Web of Science ®Google Scholar
• Zhang J, Li Y, Lu M, et al. Bone marrow stromal cells reduce axonal loss in experimental autoimmune encephalomyelitis mice. J Neurosci Res. 2006;84(3):587–595.
   PubMed Web of Science ®Google Scholar
• Cohen JA. Mesenchymal stem cell transplantation in multiple sclerosis. J Neurol Sci. 2013;333(1–2):43–49.
   PubMed Web of Science ®Google Scholar
• Bai L, Lennon DP, Eaton V, et al. Human bone marrow-derived mesenchymal stem cells induce Th2-polarized immune response and promote endogenous repair in animal models of multiple sclerosis. Glia. 2009;57(11):1192–1203.
   PubMed Web of Science ®Google Scholar
• Jafarzadeh Bejargafshe M, Hedayati M, Zahabiasli S, et al. Safety and efficacy of stem cell therapy for treatment of neural damage in patients with multiple sclerosis. Stem Cell Investig. 2019;6:44.
   PubMedGoogle Scholar
• Mauri M, Lentini D, Gravati M, et al. Mesenchymal stem cells enhance GABAergic transmission in co-cultured hippocampal neurons. Mol Cell Neurosci. 2012;49(4):395–405.
   PubMed Web of Science ®Google Scholar
• Horwitz EM, Le Blanc K, Dominici M, et al. Clarification of the nomenclature for MSC: the international society for cellular therapy position statement. Cytotherapy. 2005;7(5):393–395.
   PubMed Web of Science ®Google Scholar
• Zappia E, Casazza S, Pedemonte E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood. 2005;106(5):1755–1761.
   PubMed Web of Science ®Google Scholar
• Zhang J, Li Y, Chen J, et al. Human bone marrow stromal cell treatment improves neurological functional recovery in EAE mice. Exp Neurol. 2005;195(1):16–26.
   PubMed Web of Science ®Google Scholar
• Kassis I, Grigoriadis N, Gowda-Kurkalli B, et al. Neuroprotection and immunomodulation with mesenchymal stem cells in chronic experimental autoimmune encephalomyelitis. Arch Neurol. 2008;65(6):753–761.
   PubMedGoogle Scholar
• Seo Y, Kang MJ, Kim HS. Strategies to potentiate paracrine therapeutic efficacy of mesenchymal stem cells in inflammatory diseases. Int J Mol Sci. 2021;22(7):3397.
   Web of Science ®Google Scholar
• Kassis I, Vaknin-Dembinsky A, Karussis D. Bone marrow mesenchymal stem cells: agents of immunomodulation and neuroprotection. Curr Stem Cell Res Ther. 2011;6(1):63–68.
   PubMed Web of Science ®Google Scholar
• Douvaras P, Wang J, Zimmer M, et al. Efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells. Stem Cell Reports. 2014;3(2):250–259.
   PubMed Web of Science ®Google Scholar
• Chen B, Zhou M, Ouyang J, et al. Long-term efficacy of autologous haematopoietic stem cell transplantation in multiple sclerosis at a single institution in China. Neurol Sci. 2012;33(4):881–886.
   PubMed Web of Science ®Google Scholar
• Rice CM, Kemp K, Wilkins A, et al. Cell therapy for multiple sclerosis: an evolving concept with implications for other neurodegenerative diseases. Lancet. 2013;382(9899):1204–1213.
   PubMed Web of Science ®Google Scholar
• Riazifar M, Mohammadi MR, Pone EJ, et al. Stem Cell-Derived exosomes as nanotherapeutics for autoimmune and neurodegenerative disorders. ACS Nano. 2019;13(6):6670–6688.
   PubMed Web of Science ®Google Scholar
• Glenn JD, Smith MD, Calabresi PA, et al. Mesenchymal stem cells differentially modulate effector CD8+ T cell subsets and exacerbate experimental autoimmune encephalomyelitis. Stem Cells. 2014;32(10):2744–2755.
   PubMed Web of Science ®Google Scholar
• Mohyeddin Bonab M, Yazdanbakhsh S, Lotfi J, et al. Does mesenchymal stem cell therapy help multiple sclerosis patients? Report of a pilot study. Iran J Immunol. 2007;4(1):50–57.
   PubMedGoogle Scholar
• Yamout B, Hourani R, Salti H, et al. Bone marrow mesenchymal stem cell transplantation in patients with multiple sclerosis: a pilot study. J Neuroimmunol. 2010;227(1-2):185–189.
   PubMed Web of Science ®Google Scholar
• Odinak MM, Bisaga GN, Novitskiĭ AV, et al. Transplantation of mesenchymal stem cells in multiple sclerosis. Zh Nevrol Psikhiatr Im S S Korsakova. 2011;111(2 Pt 2):72–76.
   PubMedGoogle Scholar
• Connick P, Kolappan M, Crawley C, et al. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012;11(2):150–156.
   PubMed Web of Science ®Google Scholar
• Bonab MM, Sahraian MA, Aghsaie A, et al. Autologous mesenchymal stem cell therapy in progressive multiple sclerosis: an open label study. Curr Stem Cell Res Ther. 2012;7(6):407–414.
   PubMed Web of Science ®Google Scholar
• Lublin FD, Bowen JD, Huddlestone J, et al. 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;3(6):696–704.
   PubMed Web of Science ®Google Scholar
• Lublin FD, Reingold SC, Cohen JA, et al. Defining the clinical course of multiple sclerosis: the 2013 revisions. Neurology. 2014;83(3):278–286.
   PubMed Web of Science ®Google Scholar
• Li J-F, Zhang D-J, Geng T, et al. The potential of human umbilical cord-derived mesenchymal stem cells as a novel cellular therapy for multiple sclerosis. Cell Transplant. 2014;23 Suppl 1:S113–S22.
   PubMed Web of Science ®Google Scholar
• Cohen JA, Imrey PB, Planchon SM, et al. Pilot trial of intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Mult Scler. 2018;24(4):501–511.
   PubMed Web of Science ®Google Scholar
• Fernández O, Research Group Study EudraCT 2008-004015-35, Izquierdo G, Fernández V, et al. Adipose-derived mesenchymal stem cells (AdMSC) for the treatment of secondary-progressive multiple sclerosis: a triple blinded, placebo controlled, randomized phase I/II safety and feasibility study. PLoS One. 2018;13(5):e0195891.
   PubMed Web of Science ®Google Scholar
• Riordan NH, Morales I, Fernández G, et al. Clinical feasibility of umbilical cord tissue-derived mesenchymal stem cells in the treatment of multiple sclerosis. J Transl Med. 2018;16(1):57.
   PubMed Web of Science ®Google Scholar
• Meng M, et al. Umbilical cord mesenchymal stem cell transplantation in the treatment of multiple sclerosis. Am J Transl Res. 2018;10(1):212–223.
   PubMed Web of Science ®Google Scholar
• Sahraian MA, Mohyeddin Bonab M, Baghbanian SM, et al. Therapeutic use of intrathecal mesenchymal stem cells in patients with multiple sclerosis: a pilot study with booster injection. Immunol Invest. 2019;48(2):160–168.
   PubMed Web of Science ®Google Scholar
• Lu Z, Zhu L, Liu Z, et al. IV/IT hUC-MSCs infusion in RRMS and NMO: a 10-year follow-up study. Front Neurol. 2020;11:967.
   PubMed Web of Science ®Google Scholar
• Petrou P, Kassis I, Levin N, et al. Beneficial effects of autologous mesenchymal stem cell transplantation in active progressive multiple sclerosis. Brain. 2020;143(12):3574–3588.
   PubMed Web of Science ®Google Scholar
• Petrou P, Kassis I, Ginzberg A, et al. Long-Term clinical and immunological effects of repeated mesenchymal stem cell injections in patients with progressive forms of multiple sclerosis. Front Neurol. 2021;12:639315.
   PubMed Web of Science ®Google Scholar
• Uccelli A, MESEMS investigators, Laroni A, Ali R, et al. Safety, tolerability, and activity of mesenchymal stem cells versus placebo in multiple sclerosis (MESEMS): a phase 2, randomised, double-blind crossover trial. Lancet Neurol. 2021;20(11):917–929.
   PubMed Web of Science ®Google Scholar
• Wexler SA, Donaldson C, Denning-Kendall P, et al. Adult bone marrow is a rich source of human mesenchymal ‘stem’ cells but umbilical cord and mobilized adult blood are not. Br J Haematol. 2003;121(2):368–374.
   PubMed Web of Science ®Google Scholar
• Mizuno Y, Chang H, Umeda K, et al. Generation of skeletal muscle stem/progenitor cells from murine induced pluripotent stem cells. Faseb J. 2010;24(7):2245–2253.
   PubMed Web of Science ®Google Scholar
• Orciani M, Mariggiò MA, Morabito C, et al. Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells. Skin Pharmacol Physiol. 2010;23(3):124–132.
   PubMed Web of Science ®Google Scholar
• Hida N, Nishiyama N, Miyoshi S, et al. Novel cardiac precursor-like cells from human menstrual blood-derived mesenchymal cells. Stem Cells. 2008;26(7):1695–1704.
   PubMed Web of Science ®Google Scholar
• Gargett CE, Schwab KE, Zillwood RM, et al. Isolation and culture of epithelial progenitors and mesenchymal stem cells from human endometrium. Biol Reprod. 2009;80(6):1136–1145.
   PubMed Web of Science ®Google Scholar
• Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–147.
   PubMed Web of Science ®Google Scholar
• Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng. 2001;7(2):211–228.
   PubMedGoogle Scholar
• Ding D-C, Chang Y-H, Shyu W-C, et al. Human umbilical cord mesenchymal stem cells: a new era for stem cell therapy. Cell Transplant. 2015;24(3):339–347.
   PubMed Web of Science ®Google Scholar
• Rice CM, Mallam EA, Whone AL, et al. Safety and feasibility of autologous bone marrow cellular therapy in relapsing-progressive multiple sclerosis. Clin Pharmacol Ther. 2010;87(6):679–685.
   PubMed Web of Science ®Google Scholar
• Natsumeda M, Florea V, Rieger AC, et al. A combination of allogeneic stem cells promotes cardiac regeneration. J Am Coll Cardiol. 2017;70(20):2504–2515.
   PubMed Web of Science ®Google Scholar
• Dominici M, Le Blanc K, Mueller I, et al. Minimal criteria for defining multipotent mesenchymal stromal cells. The international society for cellular therapy position statement. Cytotherapy. 2006;8(4):315–317.
   PubMed Web of Science ®Google Scholar
• Sacchetti B, Funari A, Remoli C, et al. No identical "mesenchymal stem cells" at different times and sites: Human committed progenitors of distinct origin and differentiation potential are incorporated as adventitial cells in microvessels. Stem Cell Reports. 2016;6(6):897–913.
   PubMed Web of Science ®Google Scholar
• Oikonomopoulos A, van Deen WK, Manansala A-R, et al. Optimization of human mesenchymal stem cell manufacturing: the effects of animal/xeno-free media. Sci Rep. 2015;5:16570.
   PubMed Web of Science ®Google Scholar
• Chase LG, Lakshmipathy U, Solchaga LA, et al. A novel serum-free medium for the expansion of human mesenchymal stem cells. Stem Cell Res Ther. 2010;1(1):8.
   PubMed Web of Science ®Google Scholar
• Usta SN, Scharer CD, Xu J, et al. Chemically defined serum-free and xeno-free media for multiple cell lineages. Ann Transl Med. 2014;2(10):97.
   PubMedGoogle Scholar
• Murray IR, West CC, Hardy WR, et al. Natural history of mesenchymal stem cells, from vessel walls to culture vessels. Cell Mol Life Sci. 2014;71(8):1353–1374.
   PubMed Web of Science ®Google Scholar
• Bunnell BA, Flaat M, Gagliardi C, et al. Adipose-derived stem cells: isolation, expansion and differentiation. Methods. 2008;45(2):115–120.
   PubMed Web of Science ®Google Scholar
• François M, Copland IB, Yuan S, et al. Cryopreserved mesenchymal stromal cells display impaired immunosuppressive properties as a result of heat-shock response and impaired interferon-γ licensing. Cytotherapy. 2012;14(2):147–152.
   PubMed Web of Science ®Google Scholar
• Moll G, Alm JJ, Davies LC, et al. Do cryopreserved mesenchymal stromal cells display impaired immunomodulatory and therapeutic properties? Stem Cells. 2014;32(9):2430–2442.
   PubMed Web of Science ®Google Scholar
• Chinnadurai R, Copland IB, Garcia MA, et al. Cryopreserved mesenchymal stromal cells are susceptible to T-Cell mediated apoptosis which is partly rescued by IFNγ licensing. Stem Cells. 2016;34(9):2429–2442.
   PubMed Web of Science ®Google Scholar
• Gramlich OW, Burand AJ, Brown AJ, et al. Cryopreserved mesenchymal stromal cells maintain potency in a retinal ischemia/reperfusion injury model: toward an off-the-shelf. Sci Rep. 2016;6(1):26463.
   PubMed Web of Science ®Google Scholar
• Hoogduijn MJ, de Witte SFH, Luk F, et al. Effects of Freeze-Thawing and intravenous infusion on mesenchymal stromal cell gene expression. Stem Cells Dev. 2016;25(8):586–597.
   PubMed Web of Science ®Google Scholar
• Karussis D, Karageorgiou C, Vaknin-Dembinsky A, 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):1187–1194.
   PubMed Web of Science ®Google Scholar
• Harris VK, Vyshkina T, Sadiq SA. Clinical safety of intrathecal administration of mesenchymal stromal cell-derived neural progenitors in multiple sclerosis. Cytotherapy. 2016;18(12):1476–1482.
   PubMed Web of Science ®Google Scholar
• Kassis I, Ben-Zwi M, Petrou P, et al. Synergistic neuroprotective effects of fingolimod and mesenchymal stem cells (MSC) in experimental autoimmune encephalomyelitis. Immunol Lett. 2021;233:11–19.
   PubMed Web of Science ®Google Scholar
• Lucchinetti CF, Popescu BFG, Bunyan RF, et al. Inflammatory cortical demyelination in early multiple sclerosis. N Engl J Med. 2011;365(23):2188–2197.
   PubMed Web of Science ®Google Scholar
• Koç ON, Day J, Nieder M, et al. Allogeneic mesenchymal stem cell infusion for treatment of metachromatic leukodystrophy (MLD) and hurler syndrome (MPS-IH). Bone Marrow Transplant. 2002;30(4):215–222.
   PubMed Web of Science ®Google Scholar
• De Keyser J. Autologous mesenchymal stem cell transplantation in stroke patients. Ann Neurol. 2005;58(4):653–654. author reply 654-5.
   PubMed Web of Science ®Google Scholar
• Pal R, Venkataramana NK, Bansal A, et al. Ex vivo-expanded autologous bone marrow-derived mesenchymal stromal cells in human spinal cord injury/paraplegia: a pilot clinical study. Cytotherapy. 2009;11(7):897–911.
   PubMed Web of Science ®Google Scholar
• Ra JC, Shin IS, Kim SH, et al. Safety of intravenous infusion of human adipose tissue-derived mesenchymal stem cells in animals and humans. Stem Cells Dev. 2011;20(8):1297–1308.
   PubMed Web of Science ®Google Scholar
• Lalu MM, Canadian Critical Care Trials Group, McIntyre L, Pugliese C, et al. Safety of cell therapy with mesenchymal stromal cells (SafeCell): a systematic review and Meta-analysis of clinical trials. PLoS One. 2012;7(10):e47559.
   PubMed Web of Science ®Google Scholar
• Knoepfler PS. Deconstructing stem cell tumorigenicity: a roadmap to safe regenerative medicine. Stem Cells. 2009;27(5):1050–1056.
   PubMed Web of Science ®Google Scholar
• Mangolini M, Ringshausen I. Bone marrow stromal cells drive key hallmarks of B cell malignancies. Int J Mol Sci. 2020;21(4):1466.
   PubMed Web of Science ®Google Scholar
• Wang D, Wang S, Shi C. Update on cancer related issues of mesenchymal stem cell-based therapies. Curr Stem Cell Res Ther. 2012;7(5):370–380.
   PubMed Web of Science ®Google Scholar
• Dahbour S, Jamali F, Alhattab D, et al. Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy. CNS Neurosci Ther. 2017;23(11):866–874.
   PubMed Web of Science ®Google Scholar
• Lublin F, Miller DH, Freedman MS, et al. Oral fingolimod in primary progressive multiple sclerosis (INFORMS): a phase 3, randomised, double-blind, placebo-controlled trial. Lancet. 2016;387(10023):1075–1084.
   PubMed Web of Science ®Google Scholar
• Zhang J, Waubant E, Cutter G, et al. Composite end points to assess delay of disability progression by MS treatments. Mult Scler. 2014;20(11):1494–1501.
   PubMed Web of Science ®Google Scholar
• Cadavid D, Cohen JA, Freedman MS, et al. The EDSS-Plus, an improved endpoint for disability progression in secondary progressive multiple sclerosis. Mult Scler. 2017;23(1):94–105.
   PubMed Web of Science ®Google Scholar
• Barkhof F. The clinico-radiological paradox in multiple sclerosis revisited. Curr Opin Neurol. 2002;15(3):239–245.
   PubMed Web of Science ®Google Scholar
• Asaf A, Evan S, Anat A. Injury to white matter tracts in relapsing-remitting multiple sclerosis: a possible therapeutic window within the first 5 years from onset using diffusion-tensor imaging tract-based spatial statistics. Neuroimage Clin. 2015;8:261–266.
   PubMed Web of Science ®Google Scholar
• Feng J, Offerman E, Lin J, et al. Exploratory MRI measures after intravenous autologous culture-expanded mesenchymal stem cell transplantation in multiple sclerosis. Mult Scler J Exp Transl Clin. 2019;5(2):2055217319856035.
   Google Scholar
• Novakova L, Zetterberg H, Sundström P, et al. Monitoring disease activity in multiple sclerosis using serum neurofilament light protein. Neurology. 2017;89(22):2230–2237.
   PubMed Web of Science ®Google Scholar
• Disanto G, the Swiss Multiple Sclerosis Cohort Study Group, Barro C, Benkert P, et al. Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol. 2017;81(6):857–870.
   PubMed Web of Science ®Google Scholar
• Novakova L, Axelsson M, Khademi M, et al. Cerebrospinal fluid biomarkers as a measure of disease activity and treatment efficacy in relapsing-remitting multiple sclerosis. J Neurochem. 2017;141(2):296–304.
   PubMed Web of Science ®Google Scholar
• Kuhle J, Barro C, Disanto G, et al. Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Mult Scler. 2016;22(12):1550–1559.
   PubMed Web of Science ®Google Scholar
• Baldassari LE, Planchon SM, Bermel RA, et al. Serum neurofilament light chain concentration in a phase 1/2 trial of autologous mesenchymal stem cell transplantation. Mult Scler J Exp Transl Clin. 2019;5(4):205521731988719.
   Google Scholar
• Tafreshi AP, Payne N, Sun G, et al. Inactive GSK3β is disturbed in the spinal cord during experimental autoimmune encephalomyelitis, but rescued by stem cell therapy. Neuroscience. 2014;277:498–505.
   PubMed Web of Science ®Google Scholar
• Hou Y, Ryu CH, Park KY, et al. Effective combination of human bone marrow mesenchymal stem cells and minocycline in experimental autoimmune encephalomyelitis mice. Stem Cell Res Ther. 2013;4(4):77.
   PubMed Web of Science ®Google Scholar
• Liu R, Zhang Z, Lu Z, et al. Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination. Stem Cells Dev. 2013;22(7):1053–1062.
   PubMed Web of Science ®Google Scholar
• Strong AL, Bowles AC, Wise RM, et al. Human adipose stromal/stem cells from obese donors show reduced efficacy in halting disease progression in the experimental autoimmune encephalomyelitis model of multiple sclerosis. Stem Cells. 2016;34(3):614–626.
   PubMed Web of Science ®Google Scholar
• Donders R, Vanheusden M, Bogie JFJ, et al. Human wharton’s Jelly-Derived stem cells display immunomodulatory properties and transiently improve rat experimental autoimmune encephalomyelitis. Cell Transplant. 2015;24(10):2077–2098.
   PubMed Web of Science ®Google Scholar
• Celik DB, Poyraz EÇ, Bingöl A, et al. Sexual dysfunction ın multiple sclerosis: gender differences. J Neurol Sci. 2013;324(1-2):17–20.
   PubMed Web of Science ®Google Scholar
• Planchon SM, Lingas KT, Reese Koç J, et al. Feasibility of mesenchymal stem cell culture expansion for a phase I clinical trial in multiple sclerosis. Mult Scler J Exp Transl Clin. 2018;4(1):2055217318765288.
   Google Scholar
• Mazzanti B, Aldinucci A, Biagioli T, et al. Differences in mesenchymal stem cell cytokine profiles between MS patients and healthy donors: implication for assessment of disease activity and treatment. J Neuroimmunol. 2008;199(1-2):142–150.
   PubMed Web of Science ®Google Scholar
• Mallam E, Kemp K, Wilkins A, et al. Characterization of in vitro expanded bone marrow-derived mesenchymal stem cells from patients with multiple sclerosis. Mult Scler. 2010;16(8):909–918.
   PubMed Web of Science ®Google Scholar
• Kassis I, Petrou P, Halimi M, et al. Mesenchymal stem cells (MSC) derived from mice with experimental autoimmune encephalomyelitis (EAE) suppress EAE and have similar biological properties with MSC from healthy donors. Immunol Lett. 2013;154(1-2):70–76.
   PubMed Web of Science ®Google Scholar
• de Oliveira GLV, de Lima KWA, Colombini AM, et al. Bone marrow mesenchymal stromal cells isolated from multiple sclerosis patients have distinct gene expression profile and decreased suppressive function compared with healthy counterparts. Cell Transplant. 2015;24(2):151–165.
   PubMed Web of Science ®Google Scholar
• Kot M, et al. The importance of HLA assessment in "off-the-Shelf.” Allogeneic mesenchymal stem cells based-therapies. Int J Mol Sci. 2019;20(22):5680.
   Web of Science ®Google Scholar
• García-Sancho J, Sánchez A, Vega A, et al. Influence of HLA matching on the efficacy of allogeneic mesenchymal stromal cell therapies for osteoarthritis and degenerative disc disease. Transplant Direct. 2017;3(9):e205.
   PubMedGoogle Scholar
• Eliopoulos N, Stagg J, Lejeune L, et al. Allogeneic marrow stromal cells are immune rejected by MHC class I- and class II-mismatched recipient mice. Blood. 2005;106(13):4057–4065.
   PubMed Web of Science ®Google Scholar
• Badillo AT, Beggs KJ, Javazon EH, et al. Murine bone marrow stromal progenitor cells elicit an in vivo cellular and humoral alloimmune response. Biol Blood Marrow Transplant. 2007;13(4):412–422.
   PubMed Web of Science ®Google Scholar
• Pezzanite LM, Fortier LA, Antczak DF, et al. Equine allogeneic bone marrow-derived mesenchymal stromal cells elicit antibody responses in vivo. Stem Cell Res Ther. 2015;6(1):54.
   PubMed Web of Science ®Google Scholar
• Mansoor SR, Zabihi E, Ghasemi-Kasman M. The potential use of mesenchymal stem cells for the treatment of multiple sclerosis. Life Sci. 2019;235:116830.
   PubMed Web of Science ®Google Scholar
• Harris VK, Stark J, Vyshkina T, et al. Phase I trial of intrathecal mesenchymal stem cell-derived neural progenitors in progressive multiple sclerosis. EBioMedicine. 2018;29:23–30.
   PubMed Web of Science ®Google Scholar
• Harris VK, Faroqui R, Vyshkina T, et al. 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):536–547.
   PubMed Web of Science ®Google Scholar
• Harris VK, Stark JW, Yang S, et al. Mesenchymal stem cell-derived neural progenitors in progressive MS: Two-year follow-up of a phase I study. Neurol Neuroimmunol Neuroinflamm. 2021;8(1):e928.
   PubMed Web of Science ®Google Scholar
• Harris VK, Yan QJ, Vyshkina T, et al. Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis. J Neurol Sci. 2012;313(1-2):167–177.
   PubMed Web of Science ®Google Scholar
• Kyurkchiev D, Bochev I, Ivanova-Todorova E, et al. Secretion of immunoregulatory cytokines by mesenchymal stem cells. World J Stem Cells. 2014;6(5):552–570.
   PubMedGoogle Scholar
• Ivanova-Todorova E, Bochev I, Dimitrov R, et al. Conditioned medium from adipose tissue-derived mesenchymal stem cells induces CD4. +FOX. P3+ Cells and increases IL-10 secretion. J Biomed Biotechnol. 2012;2012:295167.
   PubMedGoogle Scholar
• Bai L, Lennon DP, Caplan AI, et al. Hepatocyte growth factor mediates mesenchymal stem cell–induced recovery in multiple sclerosis models. Nat Neurosci. 2012;15(6):862–870.
   PubMed Web of Science ®Google Scholar
• Fathollahi A, Hashemi SM, Haji Molla Hoseini M, et al. Intranasal administration of small extracellular vesicles derived from mesenchymal stem cells ameliorated the experimental autoimmune encephalomyelitis. Int Immunopharmacol. 2021;90:107207.
   PubMed Web of Science ®Google Scholar