Login Register Cart 0
Generic placeholder image

Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Review Article

Therapeutic Effects of Physical Exercise and the Mesenchymal Stem Cell Secretome by Modulating Neuroinflammatory Response in Multiple Sclerosis

Author(s): Lina María González, Laura Natalia Ospina, Laura Elena Sperling, Orlando Chaparro and Jaison Daniel Cucarián*

Volume 17, Issue 7, 2022

Published on: 18 February, 2022

Page: [621 - 632] Pages: 12

DOI: 10.2174/1574888X16666211209155333

Price: $65

conference banner
Abstract

Multiple Sclerosis (MS) is a neurodegenerative, demyelinating, and chronic inflammatory disease characterized by Central Nervous System (CNS) lesions that lead to high levels of disability and severe physical and cognitive disturbances. Conventional therapies are not enough to control the neuroinflammatory process in MS and are not able to inhibit ongoing damage to the CNS. Thus, the secretome of mesenchymal stem cells (MSC-S) has been postulated as a potential therapy that could mitigate symptoms and disease progression. We considered that its combination with physical exercise (EX) could induce superior effects and increase the MSC-S effectiveness in this condition. Recent studies have revealed that both EX and MSC-S share similar mechanisms of action that mitigate auto-reactive T cell infiltration, regulate the local inflammatory response, modulate the proinflammatory profile of glial cells, and reduce neuronal damage. Clinical and experimental studies have reported that these treatments in an isolated way also improve myelination, regeneration, promote the release of neurotrophic factors, and increase the recruitment of endogenous stem cells. Together, these effects reduce disease progression and improve patient functionality. Despite these results, the combination of these methods has not yet been studied in MS. In this review, we focus on molecular elements and cellular responses induced by these treatments in a separate way, showing their beneficial effects in the control of symptoms and disease progression in MS, as well as indicating their contribution in clinical fields. In addition, we propose the combined use of EX and MSC-S as a strategy to boost their reparative and immunomodulatory effects in this condition, combining their benefits on synaptogenesis, neurogenesis, remyelination, and neuroinflammatory response. The findings here reported are based on the scientific evidence and our professional experience that will bring significant progress to regenerative medicine to deal with this condition.

Keywords: Physical exercise, mesenchymal stem cells, secretome, multiple sclerosis, neuroinflammation, stem cell therapy.

« Previous Next »
Graphical Abstract

[1]
Koch-Henriksen N, Sørensen PS. The changing demographic pattern of multiple sclerosis epidemiology. Lancet Neurol 2010; 9(5): 520-32.
[http://dx.doi.org/10.1016/S1474-4422(10)70064-8] [PMID: 20398859]
[2]
Libert C, Dejager L, Pinheiro I. The X chromosome in immune functions: When a chromosome makes the difference. Nat Rev Immunol 2010; 10(8): 594-604.
[http://dx.doi.org/10.1038/nri2815] [PMID: 20651746]
[3]
Oh J, Vidal-Jordana A, Montalban X. Multiple sclerosis: Clinical aspects. Curr Opin Neurol 2018; 31: 752-9.
[http://dx.doi.org/10.1097/WCO.0000000000000622]
[4]
González H, Elgueta D, Montoya A, Pacheco R. Neuroimmune regulation of microglial activity involved in neuroinflammation and neurodegenerative diseases. J Neuroimmunol 2014; 274(1-2): 1-13.
[http://dx.doi.org/10.1016/j.jneuroim.2014.07.012] [PMID: 25091432]
[5]
Jelcic I, Al Nimer F, Wang J, et al. Memory B cells activate brain-homing, autoreactive CD4+ T cells in multiple sclerosis. Cell 2018; 175(1): 85-100.e23.
[http://dx.doi.org/10.1016/j.cell.2018.08.011] [PMID: 30173916]
[6]
Hartung DM. Economics and cost-effectiveness of multiple sclerosis therapies in the USA. 2017; 14(4): 1018-26.
[http://dx.doi.org/10.1007/s13311-017-0566-3] [PMID: 28812229]
[7]
Giacoppo S, Thangavelu SR, Diomede F, et al. Anti-inflammatory effects of hypoxia-preconditioned human periodontal ligament cell secretome in an experimental model of multiple sclerosis: A key role of IL-37. FASEB J 2017; 31(12): 5592-608.
[http://dx.doi.org/10.1096/fj.201700524R] [PMID: 28842429]
[8]
Cuascut FX, Hutton GJ. Stem cell-based therapies for multiple sclerosis: Current perspectives. Biomedicines MDPI AG 2019; 7(2): 26.
[http://dx.doi.org/10.3390/biomedicines7020026] [PMID: 30935074]
[9]
Akhoundzadeh K, Vakili A, Sameni HR, et al. Effects of the combined treatment of bone marrow stromal cells with mild exercise and thyroid hormone on brain damage and apoptosis in a mouse focal cerebral ischemia model. Metab Brain Dis 2017; 32(4): 1267-77.
[http://dx.doi.org/10.1007/s11011-017-0034-0] [PMID: 28547077]
[10]
Cucarián JD, Berrío JP, Rodrigues C, Zancan M, Wink MR, de Oliveira A. Physical exercise and human adipose-derived mesenchymal stem cells ameliorate motor disturbances in a male rat model of Parkinson’s disease. J Neurosci Res 2019; 97(9): 1095-109.
[http://dx.doi.org/10.1002/jnr.24442] [PMID: 31119788]
[11]
Iwanowski P, Losy J. Immunological differences between classical phenothypes of multiple sclerosis. J Neurol Sci 2015; 394(1-2): 10-4.
[http://dx.doi.org/10.1016/j.jns.2014.12.035]
[12]
Hartung DM. Health economics of disease-modifying therapy for multiple sclerosis in the United States. Ther Adv Neurol Disord 2021; 14: 1756286420987031.
[http://dx.doi.org/10.1177/1756286420987031] [PMID: 33643441]
[13]
Baranzini SE, Oksenberg JR. The genetics of multiple sclerosis: From 0 to 200 in 50 years. Trends Genet 2017; 33(12): 960-70.
[http://dx.doi.org/10.1016/j.tig.2017.09.004]
[14]
Patsopoulos NA. Genetics of multiple sclerosis: An overview and new directions. Cold Spring Harb Perspect Med 2018; 8(7): a028951.
[http://dx.doi.org/10.1101/cshperspect.a028951] [PMID: 29440325]
[15]
Guerrero-García JJ, Carrera-Quintanar L, López-Roa RI, Márquez-Aguirre AL, Rojas-Mayorquín AE, Ortuño-Sahagún D. multiple sclerosis and obesity: Possible roles of adipokines. Mediators Inflamm 2016; 2016: 4036232.
[http://dx.doi.org/10.1155/2016/4036232] [PMID: 27721574]
[16]
Degelman ML, Herman KM. Smoking and multiple sclerosis: A systematic review and meta-analysis using the Bradford Hill criteria for causation. Mult Scler Relat Disord 2017; 17: 207-16.
[http://dx.doi.org/10.1016/j.msard.2017.07.020] [PMID: 29055459]
[17]
Nardin C, Latarche C, Soudant M, et al. Generational changes in multiple sclerosis phenotype in North African immigrants in France: A population-based observational study. PLoS One 2018; 13(3): e0194115.
[http://dx.doi.org/10.1371/journal.pone.0194115] [PMID: 29584762]
[18]
Wurtman R. Multiple sclerosis, melatonin, and neurobehavioral diseases. Front Endocrinol (Lausanne) 2017; 8: 280.
[http://dx.doi.org/10.3389/fendo.2017.00280] [PMID: 29109699]
[19]
Trend S, Leffler J, Jones AP, et al. Associations of serum short-chain fatty acids with circulating immune cells and serum biomarkers in patients with multiple sclerosis. Sci Rep 2021; 11(1): 5244.
[http://dx.doi.org/10.1038/s41598-021-84881-8] [PMID: 33664396]
[20]
Guan Y, Jakimovski D, Ramanathan M, Weinstock-Guttman B, Zivadinov R. The role of Epstein-Barr virus in multiple sclerosis: From molecular pathophysiology to in vivo imaging. Neural Regen Res 2019; 14(3): 373-86.
[http://dx.doi.org/10.4103/1673-5374.245462] [PMID: 30539801]
[21]
Vallée A, Vallée JN, Guillevin R, Lecarpentier Y. Interactions between the canonical WNT/Beta-Catenin pathway and PPAR gamma on neuroinflammation, demyelination, and remyelination in multiple sclerosis. Cell Mol Neurobiol 2018; 38(4): 783-95.
[http://dx.doi.org/10.1007/s10571-017-0550-9] [PMID: 28905149]
[22]
Conradsson D, Ytterberg C, von Koch L, Johansson S. Changes in disability in people with multiple sclerosis: A 10-year prospective study. J Neurol 2018; 265(1): 119-26.
[http://dx.doi.org/10.1007/s00415-017-8676-8] [PMID: 29159465]
[23]
Coote S, Comber L, Quinn G, Santoyo-Medina C, Kalron A, Gunn H. Falls in people with multiple sclerosis: Risk identification, intervention, and future directions. Int J MS Care 2020; 22(6): 247-55.
[http://dx.doi.org/10.7224/1537-2073.2020-014] [PMID: 33424479]
[24]
Larocca NG. Impact of walking impairment in multiple sclerosis: Perspectives of patients and care partners. Patient 2011; 4(3): 189-201.
[http://dx.doi.org/10.2165/11591150-000000000-00000] [PMID: 21766914]
[25]
Peruzzi A, Cereatti A, Della Croce U, Mirelman A. Effects of a virtual reality and treadmill training on gait of subjects with multiple sclerosis: A pilot study. Mult Scler Relat Disord 2016; 5: 91-6.
[http://dx.doi.org/10.1016/j.msard.2015.11.002] [PMID: 26856951]
[26]
Kerbrat A, Gros C, Badji A, et al. Multiple sclerosis lesions in motor tracts from brain to cervical cord: Spatial distribution and correlation with disability. Brain 2020; 143(7): 2089-105.
[http://dx.doi.org/10.1093/brain/awaa162] [PMID: 32572488]
[27]
Borragán G, Gilson M, Atas A, et al. Cognitive fatigue, sleep and cortical activity in multiple sclerosis disease. A behavioral, polysomnographic and functional near-infrared spectroscopy investigation. Front Hum Neurosci 2018; 12: 378.
[http://dx.doi.org/10.3389/fnhum.2018.00378] [PMID: 30294266]
[28]
Slavkovic S, Golubovic S, Vojnovic M, Nadj C. Influence of cognitive and motor abilities on the level of current functioning in people with multiple sclerosis. Zdr Varst 2019; 58(2): 54-61.
[http://dx.doi.org/10.2478/sjph-2019-0007] [PMID: 30984295]
[29]
Magyari M, Sorensen PS. Comorbidity in multiple sclerosis. Front Neurol 2020; 11: 851.
[http://dx.doi.org/10.3389/fneur.2020.00851] [PMID: 32973654]
[30]
Louapre C, Collongues N, Stankoff B, et al. Clinical characteristics and outcomes in patients with Coronavirus disease 2019 and multiple sclerosis. JAMA Neurol 2020; 77(9): 1079-88.
[http://dx.doi.org/10.1001/jamaneurol.2020.2581] [PMID: 32589189]
[31]
Kubota T, Kuroda N. Exacerbation of neurological symptoms and COVID-19 severity in patients with preexisting neurological disorders and COVID-19: A systematic review. Clin Neurol Neurosurg 2021; 200: 106349.
[http://dx.doi.org/10.1016/j.clineuro.2020.106349] [PMID: 33172719]
[32]
Brambilla R. The contribution of astrocytes to the neuroinflammatory response in multiple sclerosis and experimental autoimmune encephalomyelitis. Acta Neuropathol 2019; 137(5): 757-83.
[http://dx.doi.org/10.1007/s00401-019-01980-7] [PMID: 30847559]
[33]
de Oliveira GLV, Ferreira AF, Gasparotto EPL, et al. Defective expression of apoptosis-related molecules in multiple sclerosis patients is normalized early after autologous haematopoietic stem cell transplantation. Clin Exp Immunol 2017; 187(3): 383-98.
[http://dx.doi.org/10.1111/cei.12895] [PMID: 28008595]
[34]
Haegert DG. Multiple sclerosis: A disorder of altered T-cell homeostasis. Mult Scler Int 2011; 2011: 461304.
[http://dx.doi.org/10.1155/2011/461304] [PMID: 22096637]
[35]
Enz LS, Zeis T, Schmid D, et al. Increased HLA-DR expression and cortical demyelination in MS links with HLA-DR15. Neurol Neuroimmunol Neuroinflamm 2019; 7(2): e656.
[http://dx.doi.org/10.1212/NXI.0000000000000656] [PMID: 31882398]
[36]
Minagar A, Alexander JS. Blood-brain barrier disruption in multiple sclerosis. Mult Scler 2003; 9(6): 540-9.
[http://dx.doi.org/10.1191/1352458503ms965oa] [PMID: 14664465]
[37]
Rempe RG, Hartz AMS, Bauer B. Matrix metalloproteinases in the brain and blood-brain barrier: Versatile breakers and makers. J Cereb Blood Flow Metab 2016; 36(9): 1481-507.
[http://dx.doi.org/10.1177/0271678X16655551] [PMID: 27323783]
[38]
Spencer JI, Bell JS, DeLuca GC. Vascular pathology in multiple sclerosis: reframing pathogenesis around the blood-brain barrier. J Neurol Neurosurg Psychiatry 2018; 89(1): 42-52.
[http://dx.doi.org/10.1136/jnnp-2017-316011] [PMID: 28860328]
[39]
Ramaglia V, Rojas O, Naouar I, Gommerman JL. The ins and outs of central nervous system inflammation-lessons learned from multiple sclerosis. Annu Rev Immunol 2021; 39(1): 199-226.
[http://dx.doi.org/10.1146/annurev-immunol-093019-124155] [PMID: 33524273]
[40]
Dalla Costa G, Martinelli V, Sangalli F, et al. Prognostic value of serum neurofilaments in patients with clinically isolated syndromes. Neurology 2019; 92(7): e733-41.
[http://dx.doi.org/10.1212/WNL.0000000000006902] [PMID: 30635483]
[41]
Lee JY, Taghian K, Petratos S. Axonal degeneration in multiple sclerosis: Can we predict and prevent permanent disability? Acta Neuropathol Commun 2014; 2: 97.
[http://dx.doi.org/10.1186/s40478-014-0097-7] [PMID: 25159125]
[42]
Refolo V, Stefanova N. Neuroinflammation and glial phenotypic changes in alpha-synucleinopathies. Front Cell Neurosci 2019; 13: 263.
[http://dx.doi.org/10.3389/fncel.2019.00263] [PMID: 31263402]
[43]
Correale J, Marrodan M, Ysrraelit MC. Mechanisms of neurodegeneration and axonal dysfunction in progressive multiple sclerosis. Biomedicines MDPI AG 2019; 7(1): 14.
[http://dx.doi.org/10.3390/biomedicines7010014] [PMID: 30791637]
[44]
Naegele M, Martin R. The good and the bad of neuroinflammation in multiple sclerosis. Handb Clin Neuro 2014; 122: 59-87.
[http://dx.doi.org/10.1016/B978-0-444-52001-2.00003-0]
[45]
Małkiewicz MA, Szarmach A, Sabisz A, Cubała WJ, Szurowska E, Winklewski PJ. Blood-brain barrier permeability and physical exercise. J Neuroinflam 2019; 16(1): 15.
[http://dx.doi.org/10.1186/s12974-019-1403-x] [PMID: 30678702]
[46]
Stillman CM, Esteban-Cornejo I, Brown B, Bender CM, Erickson KI. Effects of exercise on brain and cognition across age groups and health states. Trends Neurosci 2020; 43(7): 533-43.
[http://dx.doi.org/10.1016/j.tins.2020.04.010] [PMID: 32409017]
[47]
Di Liegro CM, Schiera G, Proia P, Di Liegro I. Physical activity and brain health. Genes (Basel) 2019; 10(9): 720.
[http://dx.doi.org/10.3390/genes10090720] [PMID: 31533339]
[48]
Xie Y, Li Z, Wang Y, et al. Effects of moderate- versus high- intensity swimming training on inflammatory and CD4+ T cell subset profiles in experimental autoimmune encephalomyelitis mice. J Neuroimmunol 2019; 328: 60-7.
[http://dx.doi.org/10.1016/j.jneuroim.2018.12.005] [PMID: 30583216]
[49]
Campbell JP, Turner JE. Debunking the myth of exercise-induced immune suppression: Redefining the impact of exercise on immunological health across the lifespan. Front Immunol 2018; 9: 648.
[http://dx.doi.org/10.3389/fimmu.2018.00648] [PMID: 29713319]
[50]
Terra R, da Silva SAG, Pinto VS, Dutra PML. Effect of exercise on the immune system: Response, adaptation and cell signaling. revista brasileira de medicina do esporte. Rev Bras Med Esporte 2012; 18: 208-14.
[http://dx.doi.org/10.1590/S1517-86922012000300015]
[51]
Abbaspoor E, Zolfaghari M, Ahmadi B, Khodaei K. The effect of combined functional training on BDNF, IGF-1, and their association with health-related fitness in the multiple sclerosis women. Growth Horm IGF Res 2020; 52: 101320.
[http://dx.doi.org/10.1016/j.ghir.2020.101320] [PMID: 32305012]
[52]
Svensson M, Lexell J, Deierborg T. Effects of physical exercise on neuroinflammation, neuroplasticity, neurodegeneration, and behavior: What we can learn from animal models in clinical settings. Neurorehabil Neural Repair 2015; 29(6): 577-89.
[http://dx.doi.org/10.1177/1545968314562108] [PMID: 25527485]
[53]
Deckx N, Wens I, Nuyts AH, et al. 12 weeks of combined endurance and resistance training reduces innate markers of inflammation in a randomized controlled clinical trial in patients with multiple sclerosis. Mediators Inflamm 2016; 2016: 6789276.
[http://dx.doi.org/10.1155/2016/6789276] [PMID: 26903712]
[54]
Mokhtarzade M, Motl R, Negaresh R, et al. Exercise-induced changes in neurotrophic factors and markers of blood-brain barrier permeability are moderated by weight status in multiple sclerosis. Neuropeptides 2018; 70: 93-100.
[http://dx.doi.org/10.1016/j.npep.2018.05.010] [PMID: 29880392]
[55]
Souza PS, Gonçalves ED, Pedroso GS, et al. Physical exercise attenuates experimental autoimmune encephalomyelitis by inhibiting peripheral immune response and blood-brain barrier disruption. Mol Neurobiol 2017; 54(6): 4723-37.
[http://dx.doi.org/10.1007/s12035-016-0014-0] [PMID: 27447807]
[56]
Huppert J, Closhen D, Croxford A, et al. Cellular mechanisms of IL-17-induced blood-brain barrier disruption. FASEB J 2010; 24(4): 1023-34.
[http://dx.doi.org/10.1096/fj.09-141978] [PMID: 19940258]
[57]
Berkowitz S, Achiron A, Gurevich M, Sonis P, Kalron A. Acute effects of aerobic intensities on the cytokine response in women with mild multiple sclerosis. Mult Scler Relat Disord 2019; 31: 82-6.
[http://dx.doi.org/10.1016/j.msard.2019.03.025] [PMID: 30951969]
[58]
Negaresh R, Motl RW, Zimmer P, Mokhtarzade M, Baker JS. Effects of exercise training on multiple sclerosis biomarkers of central nervous system and disease status: A systematic review of intervention studies. Eur J Neurol 2019; 26(5): 711-21.
[http://dx.doi.org/10.1111/ene.13929] [PMID: 30734989]
[59]
Donia SA, Allison DJ, Gammage KL, Ditor DS. The effects of acute aerobic exercise on mood and inflammation in individuals with multiple sclerosis and incomplete spinal cord injury. NeuroRehabilitation 2019; 45(1): 117-24.
[http://dx.doi.org/10.3233/NRE-192773] [PMID: 31450521]
[60]
Nieman DC, Wentz LM. The compelling link between physical activity and the body’s defense system. J Sport Health Sci 2019; 8(3): 201-17.
[http://dx.doi.org/10.1016/j.jshs.2018.09.009] [PMID: 31193280]
[61]
Maas DA, Angulo MC. Can enhancing neuronal activity improve myelin repair in multiple sclerosis?? Front Cell Neurosci 2021; 15: 645240.
[http://dx.doi.org/10.3389/fncel.2021.645240] [PMID: 33708075]
[62]
Feter N, Freitas MP, Gonzales NG, Umpierre D, Cardoso RK, Rombaldi AJ. Effects of physical exercise on myelin sheath regeneration: A systematic review and meta-analysis. Science and Sports. Elsevier Masson SAS 2018; 33: 8-21.
[http://dx.doi.org/10.1016/j.scispo.2017.06.009]
[63]
Li R, Li DH, Zhang HY, Wang J, Li XK, Xiao J. Growth factors-based therapeutic strategies and their underlying signaling mechanisms for peripheral nerve regeneration. Acta Pharmacol Sin 2020; 41(10): 1289-300.
[http://dx.doi.org/10.1038/s41401-019-0338-1] [PMID: 32123299]
[64]
Ozkul C, Guclu-Gunduz A, Irkec C, et al. Effect of combined exercise training on serum brain-derived neurotrophic factor, suppressors of cytokine signaling 1 and 3 in patients with multiple sclerosis. J Neuroimmunol 2018; 316(316): 121-9.
[http://dx.doi.org/10.1016/j.jneuroim.2018.01.002] [PMID: 29329698]
[65]
Wens I, Keytsman C, Deckx N, Cools N, Dalgas U, Eijnde BO. Brain derived neurotrophic factor in multiple sclerosis: Effect of 24 weeks endurance and resistance training. Eur J Neurol 2016; 23(6): 1028-35.
[http://dx.doi.org/10.1111/ene.12976] [PMID: 26992038]
[66]
Sleiman SF, Henry J, Al-Haddad R, et al. Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. eLife 2016; 5: e15092.
[http://dx.doi.org/10.7554/eLife.15092] [PMID: 27253067]
[67]
Gentile A, Musella A, De Vito F, et al. Immunomodulatory effects of exercise in experimental multiple sclerosis. Front Immunol 2019; 10: 2197.
[http://dx.doi.org/10.3389/fimmu.2019.02197] [PMID: 31572399]
[68]
Arany Z. PGC-1 coactivators and skeletal muscle adaptations in health and disease. Curr Opin Genet Dev 2008; 18(5): 426-34.
[http://dx.doi.org/10.1016/j.gde.2008.07.018] [PMID: 18782618]
[69]
Mills R, Taylor-Weiner H, Correia JC, et al. Neurturin is a PGC-1α1-controlled myokine that promotes motor neuron recruitment and neuromuscular junction formation. Mol Metab 2018; 7: 12-22.
[http://dx.doi.org/10.1016/j.molmet.2017.11.001] [PMID: 29157948]
[70]
Collao N, Rada I, Francaux M, Deldicque L, Zbinden-Foncea H. Anti-inflammatory effect of exercise mediated by Toll-like receptor regulation in innate immune cells. Int Rev Immunol 2020; 39(2): 39-52.
[http://dx.doi.org/10.1080/08830185.2019.1682569] [PMID: 31682154]
[71]
Zaychik Y, Fainstein N, Touloumi O, et al. high-intensity exercise training protects the brain against autoimmune neuroinflammation: regulation of microglial redox and pro-inflammatory functions. Front Cell Neurosci 2021; 15: 640724.
[http://dx.doi.org/10.3389/fncel.2021.640724] [PMID: 33708074]
[72]
Grazioli E, Tranchita E, Borriello G, Cerulli C, Minganti C, Parisi A. The effects of concurrent resistance and aerobic exercise training on functional status in patients with multiple sclerosis. Curr Sports Med Rep 2019; 18(12): 452-7.
[http://dx.doi.org/10.1249/JSR.0000000000000661] [PMID: 31834177]
[73]
Mifflin KA, Frieser E, Benson C, Baker G, Kerr BJ. Voluntary wheel running differentially affects disease outcomes in male and female mice with experimental autoimmune encephalomyelitis. J Neuroimmunol 2017; 305: 135-44.
[http://dx.doi.org/10.1016/j.jneuroim.2017.02.005] [PMID: 28284334]
[74]
Mifflin KA, Yousuf MS, Thorburn KC, et al. Voluntary wheel running reveals sex-specific nociceptive factors in murine experimental autoimmune encephalomyelitis. Pain 2019; 160(4): 870-81.
[http://dx.doi.org/10.1097/j.pain.0000000000001465] [PMID: 30540622]
[75]
Gubert C, Kong G, Renoir T, Hannan AJ. Exercise, diet and stress as modulators of gut microbiota: Implications for neurodegenerative diseases. Neurobiol Dis 2020; 134: 4621.
[http://dx.doi.org/10.1016/j.nbd.2019.104621]
[76]
Chu F, Shi M, Lang Y, et al. Gut microbiota in multiple sclerosis and experimental autoimmune encephalomyelitis: Current applications and future perspectives. Mediat Inflamm 2018; 2018: 8168717.
[http://dx.doi.org/10.1155/2018/8168717] [PMID: 29805314]
[77]
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): 250-9.
[http://dx.doi.org/10.1016/j.stemcr.2014.06.012] [PMID: 25254339]
[78]
Mansilla MJ, Presas-Rodríguez S, Teniente-Serra A, et al. Paving the way towards an effective treatment for multiple sclerosis: Advances in cell therapy. Cell Mol Immunol 2021; 18(6): 1353-74.
[http://dx.doi.org/10.1038/s41423-020-00618-z] [PMID: 33958746]
[79]
Genc B, Bozan HR, Genc S, Genc K. Stem cell therapy for multiple sclerosis.Adv Exp Med Biol. 2019; 1084: pp. 145-74.
[http://dx.doi.org/10.1007/5584_2018_247]
[80]
Shroff G. A review on stem cell therapy for multiple sclerosis: special focus on human embryonic stem cells. Stem Cells Cloning 2018; 11: 1-11.
[http://dx.doi.org/10.2147/SCCAA.S135415] [PMID: 29483778]
[81]
Harris VK, Yan QJ, Vyshkina T, Sahabi S, Liu X, Sadiq SA. 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): 167-77.
[http://dx.doi.org/10.1016/j.jns.2011.08.036] [PMID: 21962795]
[82]
Karussis D, Kassis I, Kurkalli BGS, Slavin S. Immunomodulation and neuroprotection with mesenchymal bone marrow stem cells (MSCs): A proposed treatment for multiple sclerosis and other neuroimmunological/neurodegenerative diseases. J Neurol Sci 2008; 265(1-2): 131-5.
[http://dx.doi.org/10.1016/j.jns.2007.05.005] [PMID: 17610906]
[83]
Marin-Bañasco C, Benabdellah K, Melero-Jerez C, et al. Gene therapy with mesenchymal stem cells expressing IFN-ß ameliorates neuroinflammation in experimental models of multiple sclerosis. Br J Pharmacol 2017; 174(3): 238-53.
[http://dx.doi.org/10.1111/bph.13674] [PMID: 27882538]
[84]
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.
[http://dx.doi.org/10.1186/s12967-018-1433-7] [PMID: 29523171]
[85]
Damasceno PKF, de Santana TA, Santos GC, et al. Genetic engineering as a strategy to improve the therapeutic efficacy of mesenchymal stem/stromal cells in regenerative medicine. Front Cell Dev Biol 2020; 8: 737.
[http://dx.doi.org/10.3389/fcell.2020.00737] [PMID: 32974331]
[86]
Darlington PJ, Stopnicki B, Touil T, et al. Natural killer cells regulate Th17 cells after autologous hematopoietic stem cell transplantation for relapsing remitting multiple sclerosis. Front Immunol 2018; 9: 834.
[http://dx.doi.org/10.3389/fimmu.2018.00834] [PMID: 29867923]
[87]
Vizoso FJ, Eiro N, Cid S, Schneider J, Perez-Fernandez R. Mesenchymal stem cell secretome: Toward cell-free therapeutic strategies in regenerative medicine. Sci Int J Mol Sci 2017; 18(9): E1852.
[http://dx.doi.org/10.3390/ijms18091852] [PMID: 28841158]
[88]
Baharlooi H, Azimi M, Salehi Z, Izad M. Mesenchymal stem cell-derived exosomes: A promising therapeutic ace card to address autoimmune diseases. Int J Stem Cells 2020; 13(1): 13-23.
[http://dx.doi.org/10.15283/ijsc19108] [PMID: 31887849]
[89]
Baez-Jurado E, Hidalgo-Lanussa O, Barrera-Bailón B, Sahebkar A, Ashraf GM, Echeverria V. Secretome of mesenchymal stem cells and its potential protective effects on brain pathologies. Mol Neurobiol 2019; 56: 6902-27.
[http://dx.doi.org/10.1007/s12035-019-1570-x]
[90]
Li Z, Liu F, He X, Yang X, Shan F, Feng J. Exosomes derived from mesenchymal stem cells attenuate inflammation and demyelination of the central nervous system in EAE rats by regulating the polarization of microglia. Int Immunopharmacol 2019; 67(67): 268-80.
[http://dx.doi.org/10.1016/j.intimp.2018.12.001] [PMID: 30572251]
[91]
Yan L, Jiang B, Niu Y, et al. Intrathecal delivery of human ESC-derived mesenchymal stem cell spheres promotes recovery of a primate multiple sclerosis model. Cell Death Discov 2018; 4: 28.
[http://dx.doi.org/10.1038/s41420-018-0091-0] [PMID: 30131877]
[92]
Rajan TS, Giacoppo S, Diomede F, et al. The secretome of periodontal ligament stem cells from MS patients protects against EAE. Sci Rep 2016; 6: 38743.
[http://dx.doi.org/10.1038/srep38743] [PMID: 27924938]
[93]
Martins LF, Costa RO, Pedro JR, et al. Mesenchymal stem cells secretome-induced axonal outgrowth is mediated by BDNF. Sci Rep 2017; 7(1): 4153.
[http://dx.doi.org/10.1038/s41598-017-03592-1] [PMID: 28646200]
[94]
Bermudez MA, Sendon-Lago J, Seoane S, et al. Anti-inflammatory effect of conditioned medium from human uterine cervical stem cells in uveitis. Exp Eye Res 2016; 149: 84-92.
[http://dx.doi.org/10.1016/j.exer.2016.06.022] [PMID: 27381329]
[95]
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.
[http://dx.doi.org/10.3390/cells8050467] [PMID: 31100966]
[96]
Zagoura DS, Roubelakis MG, Bitsika V, et al. Therapeutic potential of a distinct population of human amniotic fluid mesenchymal stem cells and their secreted molecules in mice with acute hepatic failure. Gut 2012; 61(6): 894-906.
[http://dx.doi.org/10.1136/gutjnl-2011-300908] [PMID: 21997562]
[97]
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): 866-74.
[http://dx.doi.org/10.1111/cns.12759] [PMID: 28961381]
[98]
Arruda LCM, de Azevedo JTC, de Oliveira GLV, et al. Immunological correlates of favorable long-term clinical outcome in multiple sclerosis patients after autologous hematopoietic stem cell transplantation. Clin Immunol 2016; 169: 47-57.
[http://dx.doi.org/10.1016/j.clim.2016.06.005] [PMID: 27318116]
[99]
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): 185-9.
[http://dx.doi.org/10.1016/j.jneuroim.2010.07.013] [PMID: 20728948]
[100]
Fan XL, Zhang Y, Li X, Fu QL. Mechanisms underlying the protective effects of mesenchymal stem cell-based therapy. Cell Mol Life Sci 2020; 77(14): 2771-94.
[http://dx.doi.org/10.1007/s00018-020-03454-6] [PMID: 31965214]
[101]
Yan L, Zheng D, Xu RH. Critical role of tumor necrosis factor signaling in mesenchymal stem cell-based therapy for autoimmune and inflammatory diseases. Frontiers in Immunology. Front Immunol 2018; 9: 1658.
[http://dx.doi.org/10.3389/fimmu.2018.01658] [PMID: 30079066]
[102]
Akiyama K, Chen C, Wang D, et al. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell 2012; 10(5): 544-55.
[http://dx.doi.org/10.1016/j.stem.2012.03.007] [PMID: 22542159]
[103]
Sarkar P, Redondo J, Kemp K, et al. Reduced neuroprotective potential of the mesenchymal stromal cell secretome with ex vivoexpansion, age and progressive multiple sclerosis. Cytotherapy 2018; 20(1): 21-8.
[http://dx.doi.org/10.1016/j.jcyt.2017.08.007] [PMID: 28917625]
[104]
Pusic AD, Kraig RP. Youth and environmental enrichment generate serum exosomes containing miR-219 that promote CNS myelination. Glia 2014; 62(2): 284-99.
[http://dx.doi.org/10.1002/glia.22606] [PMID: 24339157]
[105]
Bourzac C, Bensidhoum M, Pallu S, Portier H. Use of adult mesenchymal stromal cells in tissue repair: Impact of physical exercise. Am J Physiol Cell Physiol 2019; 317: C642-54.
[http://dx.doi.org/10.1152/ajpcell.00530.2018]
[106]
Marędziak M, Śmieszek A, Chrząstek K, Basinska K, Marycz K. Physical activity increases the total number of bone-marrow-derived mesenchymal stem cells, enhances their osteogenic potential, and inhibits their adipogenic properties. Stem Cells Int 2015; 2015: 379093.
[http://dx.doi.org/10.1155/2015/379093] [PMID: 26167185]
[107]
Emmons R, Niemiro GM, Owolabi O, De Lisio M. Acute exercise mobilizes hematopoietic stem and progenitor cells and alters the mesenchymal stromal cell secretome. J Appl Physiol 2016; 120(6): 624-32.
[http://dx.doi.org/10.1152/japplphysiol.00925.2015] [PMID: 26744505]
[108]
Abshenas R, Artimani T, Shahidi S, et al. Treadmill exercise enhances the promoting effects of preconditioned stem cells on memory and neurogenesis in Aβ-induced neurotoxicity in the rats. Life Sci 2020; 249: 117482.
[http://dx.doi.org/10.1016/j.lfs.2020.117482] [PMID: 32135186]
[109]
Morishita S, Tsubaki A, Hotta K, Fu JB, Fuji S. The benefit of exercise in patients who undergo allogeneic hematopoietic stem cell transplantation. J Int Soc Phys Rehabil Med 2019; 2(1): 54-61.
[http://dx.doi.org/10.4103/jisprm.jisprm_2_19] [PMID: 31131374]
[110]
Steinberg A, Asher A, Bailey C, Fu JB. The role of physical rehabilitation in stem cell transplantation patients. Support Care Cancer 2015; 23: 2447-60.
[http://dx.doi.org/10.1007/s00520-015-2744-3]

Rights & Permissions Print Cite
Article Metrics
19
1
© 2024 Bentham Science Publishers | Privacy Policy