Generic placeholder image

Current Stem Cell Research & Therapy

Author(s): Miguel Antonio Jiménez-Acosta, Lory Jhenifer Rochin Hernández, Mayte Lizeth Padilla Cristerna and Marco Alejandro Meraz-Ríos*

DOI: 10.2174/1574888X17666220511153133

DownloadDownload PDF Flyer Cite As
Mesenchymal Stem Cells: New Alternatives for Nervous System Disorders

Page: [299 - 321] Pages: 23

  • * (Excluding Mailing and Handling)

Abstract

Mesenchymal stem cells (MSCs) are self-renewing cells found in almost all postnatal organs and tissues in the perivascular region. These cells have a high capacity for mesodermal differentiation; however, numerous studies have shown that MSCs can also differentiate into cells of endodermal and ectodermal lineages. Due to this multilineage differentiation capacity, these cells could function as restoratives of various cell populations after transplantation. However, not only their differentiation potential makes them ideal candidates for this, but also a series of trophic properties that promote regeneration in the surrounding tissue, such as their migratory capacity, secretory and immunomodulatory actions. This review analyzes several MSC transplantation trials to treat neurological diseases, such as demyelinating injury, spinal cord injury, paraplegia, Parkinson's disease, cochlear injury, and Alzheimer's disease. These cells could facilitate functional recovery in multiple models of neurodegenerative diseases and nervous system injuries by using their trophic capacities, reducing inflammation in the injured area, reducing apoptosis, and enhancing endogenous neurogenesis through the secretion of bioactive factors. Furthermore, since cells derived from patients have demonstrated disease-associated differences in various brain diseases, these cells represent an excellent candidate for the study of these diseases, functioning as "a window to the brain."

Keywords: : Mesenchymal stem cells, Nervous system disorders, Neurodegenerative diseases, Transplantation, Cell-based therapy, Neuronal differentiation, Functional recovery.

Graphical Abstract

[1]
Ahuja CS, Mothe A, Khazaei M, Badhiwala JH, Gilbert EA, Kooy D, et al. The leading edge: Emerging neuroprotective and neuroregenerative cell based therapies for spinal cord injury. Stem Cells Transl Med 2020; 9(12): 1509-30.https://onlinelibrary.wiley.com/doi/abs/10.1002/sctm.19-0135
[2]
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): 315-7.
[http://dx.doi.org/10.1080/14653240600855905] [PMID: 16923606]
[3]
Patel DM, Shah J, Srivastava AS. Therapeutic potential of mesenchymal stem cells in regenerative medicine. Stem Cells Int 2013; 2013: 496218.
[http://dx.doi.org/10.1155/2013/496218] [PMID: 23577036]
[4]
Friedenstein AJ, Piatetzky SI, Petrakova KV. Osteogenesis intransplants of bone marrow cells. Embryol exp Morph 1966; 16: 581-390.
[5]
Friedenstein AJ, Chailakhjan RK, Lalykina KS. The development of fibroblast colonies in monolayer cultures of guinea-pig bone marrow and spleen cells. Cell Tissue Kinet 1970; 3(4): 393-403.
[http://dx.doi.org/10.1111/j.1365-2184.1970.tb00347.x] [PMID: 5523063]
[6]
Friedenstein AJ, Chailakhyan RK, Gerasimov UV. Bone marrow osteogenic stem cells: In vitro cultivation and transplantation in diffusion chambers. Cell Tissue Kinet 1987; 20(3): 263-72.
[http://dx.doi.org/10.1111/j.1365-2184.1987.tb01309.x] [PMID: 3690622]
[7]
Caplan AI. Mesenchymal stem cells. J Orthop Res 1991; 9(5): 641-50.
[http://dx.doi.org/10.1002/jor.1100090504] [PMID: 1870029]
[8]
Pittenger MF. Multilineage Potential of adult human mesenchymal stem cells. Science 1999; 284(5411): 143-7.
[http://dx.doi.org/10.1126/science.284.5411.143]
[9]
Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue: implications for cell-based therapies. (Tissue Eng)2001; 7(2): 211-8.https://pubmed.ncbi.nlm.nih.gov/11304456/
[http://dx.doi.org/10.1089/107632701300062859] [PMID: 11304456]
[10]
Socarrás F. Células madre mesenquimales: aspectos relevantes y aplicación clínica en la medicina regenerativa. 2013. Available from: http://scielo.sld.cu/scielo.php?script=sci_arttext&pid=S0864- 02892013000100003
[11]
Bernardo ME, Pagliara D, Locatelli F. Mesenchymal stromal cell therapy: A revolution in regenerative medicine? Bone Marrow Transplant 2012; 47(2): 164-71.https://pubmed.ncbi.nlm.nih.gov/21478914/
[http://dx.doi.org/10.1038/bmt.2011.81] [PMID: 21478914]
[12]
Jackson WM, Nesti LJ, Tuan RS. Potential therapeutic applications of muscle-derived mesenchymal stem and progenitor cells. Expert Opin Bio The 2010; 10(4): 505-17. Available from: https://pmc/articles/PMC3018682/?report=abstract
[13]
Chen PM, Yen ML, Liu KJ, Sytwu HK, Yen BL. Immunomodulatory properties of human adult and fetal multipotent mesenchymal stem cells. J Biomed Sci Bio Med Central 2011; 18: 18-49. Available from: http://www.jbiomedsci.com/content/18/1/49
[14]
Bas E, Van De WTR, Lumbreras V, et al. Adult human nasal mesenchymal-like stem cells restore cochlear spiral ganglion neurons after experimental lesion. Stem Cells Dev 2014; 23(5): 502-14.
[http://dx.doi.org/10.1089/scd.2013.0274] [PMID: 24172073]
[15]
Delorme B, Nivet E, Gaillard J, et al. The human nose harbors a niche of olfactory ectomesenchymal stem cells displaying neurogenic and osteogenic properties. Stem Cells Dev 2010; 19(6): 853-66.
[http://dx.doi.org/10.1089/scd.2009.0267] [PMID: 19905894]
[16]
Kern S, Eichler H, Stoeve J, Klüter H, Bieback K. Comparative analysis of mesenchymal stem cells from bone marrow, umbilical cord blood, or adipose tissue. Stem Cells 2006; 24(5): 1294-301.https://stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1634/stemcells.2005-0342
[http://dx.doi.org/10.1634/stemcells.2005-0342] [PMID: 16410387]
[17]
Lukomska B, Stanaszek L, Zuba SE, Legosz P, Sarzynska S, Drela K. Challenges and controversies in human mesenchymal stem cell therapy. stem cells international. Hindawi Limited 2019; 2019: 9628536.
[18]
Lee KD, Kuo TKC, Whang PJ, et al. In vitro hepatic differentiation of human mesenchymal stem cells Hepatology 2004; 40(6): 1275-84.https://pubmed.ncbi.nlm.nih.gov/15562440/
[http://dx.doi.org/10.1002/hep.20469] [PMID: 15562440]
[19]
Chen LB, Jiang XB, Yang L. Differentiation of rat marrow mesenchymal stem cells into pancreatic islet beta-cells. World J Gastroenterol 2004; 10(20): 3016-20. Available from: https://pmc/articles/PMC4576264/?report=abstract
[http://dx.doi.org/10.3748/wjg.v10.i20.3016]
[20]
Shi Y, Hu Y, Lv C, Tu G. Effects of reactive oxygen species on differentiation of bone marrow mesenchymal stem cells. Ann Transplant 2016; 21: 695-700.
[http://dx.doi.org/10.12659/AOT.900463] [PMID: 27840405]
[21]
Ayala GC, Pieruzzini R, Vargas SL, Cardier JE. Human olfactory mesenchymal stromal cells co-expressing horizontal basal and ensheathing cell proteins in culture. Biomédica 2020; 40(1): 72-88.
[http://dx.doi.org/10.7705/biomedica.4762] [PMID: 32220165]
[22]
Ying C, Hu W, Cheng B, Zheng X, Li S. Neural differentiation of rat adipose-derived stem cells in vitro. Cell Mol Neurobiol 2012; 32(8): 1255-63.https://link.springer.com/article/10.1007/s10571-012-9850-2
[http://dx.doi.org/10.1007/s10571-012-9850-2] [PMID: 22569742]
[23]
Tremain N, Korkko J, Ibberson D, Kopen GC, DiGirolamo C, Phinney DG. MicroSAGE analysis of 2,353 expressed genes in a single cell-derived colony of undifferentiated human mesenchymal stem cells reveals mRNAs of multiple cell lineages. Stem Cells 2001; 19(5): 408-18.https://pubmed.ncbi.nlm.nih.gov/11553849/
[http://dx.doi.org/10.1634/stemcells.19-5-408] [PMID: 11553849]
[24]
Weiss ML, Medicetty S, Bledsoe AR, et al. Human umbilical cord matrix stem cells: preliminary characterization and effect of transplantation in a rodent model of Parkinson’s disease. Stem Cells 2006; 24(3): 781-92.
[http://dx.doi.org/10.1634/stemcells.2005-0330] [PMID: 16223852]
[25]
Zhong C, Qin Z, Zhong CJ, Wang Y, Shen XY. Neuroprotective effects of bone marrow stromal cells on rat organotypic hippocampal slice culture model of cerebral ischemia. Neurosci Lett 2003; 342(1-2): 93-6.
[http://dx.doi.org/10.1016/S0304-3940(03)00255-6] [PMID: 12727326]
[26]
Isabel M, De León GA, Roche E, En Biología LC, Santana RA. Differential plasticity of different clones of mesenchymal stem cells isolated from human lipoaspiratesMeraz-Rios-CSCRT-2021-171-MS.docx 2011. Available from [https://dspace-umhes. translate.goog/handle/11000/1680?_x_tr_sch=http&_x_tr_sl=es &_x_tr_tl=en&_x_tr_hl=en&_x_tr_pto=sc]
[27]
Aggarwal S, Pittenger MF. Human mesenchymal stem cells modulate allogeneic immune cell responses. Blood 2005; 105(4): 1815-22.http://ashpublications.org/blood/article-pdf/105/4/1815/1707068/zh800405001815.pdf
[http://dx.doi.org/10.1182/blood-2004-04-1559] [PMID: 15494428]
[28]
Chen X, Katakowski M, Li Y, et al. Human bone marrow stromal4 cell cultures conditioned by traumatic brain tissue extracts: growth factor production. J Neurosci Res 2002; 69(5): 687-91.http://doi.wiley.com/10.1002/jnr.10334
[http://dx.doi.org/10.1002/jnr.10334] [PMID: 12210835]
[29]
Himes BT, Neuhuber B, Coleman C, et al. Recovery of function following grafting of human bone marrow-derived stromal cells into the injured spinal cord. Neurorehabil Neural Repair 2006; 20(2): 278-96.
[http://dx.doi.org/10.1177/1545968306286976] [PMID: 16679505]
[30]
Xun C, Ge L, Tang F, et al. Insight into the proteomic profiling of exosomes secreted by human OM-MSCs reveals a new potential therapy. Biomed Pharmacother 2020; 131: 110584.
[http://dx.doi.org/10.1016/j.biopha.2020.110584] [PMID: 32841894]
[31]
Xin H, Li Y, Liu Z, et al. MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 2013; 31(12): 2737-46.https://pubmed.ncbi.nlm.nih.gov/23630198/
[http://dx.doi.org/10.1002/stem.1409] [PMID: 23630198]
[32]
Liu WG, Wang ZY, Huang ZS. Bone marrow-derived mesenchymal stem cells expressing the bFGF transgene promote axon regeneration and functional recovery after spinal cord injury in rats Neurol res 2011; 33(7): 686-93.http://pubmed.ncbi.nlm.nih.gov/21756547/
[http://dx.doi.org/10.1179/1743132810Y.0000000031] [PMID: 21756547]
[33]
Rooney GE, McMahon SS, Ritter T, et al. Neurotrophic factorexpressing mesenchymal stem cells survive transplantation into the contused spinal cord without differentiating into neural cells. Tissue Eng Part A 2009; 15(10): 3049-59.https://pubmed.ncbi.nlm.nih.gov/19335061/
[http://dx.doi.org/10.1089/ten.tea.2009.0045] [PMID: 19335061]
[34]
Kim YH, Cho SH, Lee SJ, et al. Growth-inhibitory effect of neurotrophin- 3-secreting adipose tissue-derived mesenchymal stem cells on the D283-MED human medulloblastoma cell line. J Neurooncol 2012; 106(1): 89-98.https://pubmed.ncbi.nlm.nih.gov/21720807/
[http://dx.doi.org/10.1007/s11060-011-0656-8] [PMID: 21720807]
[35]
Jin M, Chen Y, Zhou Y, et al. Transplantation of bone marrowderived mesenchymal stem cells expressing elastin alleviates pelvic floor dysfunction. Stem Cell Res Ther 2016; 7(1): 51.http://stemcellres.biomedcentral.com/articles/10.1186/s13287-016-0308-1
[http://dx.doi.org/10.1186/s13287-016-0308-1] [PMID: 27048404]
[36]
Klein A, Barsky LW, Wu G, et al. The role of the hyaluronan receptor cd44 in mesenchymal stem cell migration in the extracellular matrix. Stem Cells 2006; 24(4): 928-35. Available from:http://www.promega.com
[37]
Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA 1999; 96(19): 10711-6.
[http://dx.doi.org/10.1073/pnas.96.19.10711]
[38]
Azizi SA, Stokes D, Augelli BJ, DiGirolamo C, Prockop DJ. Engraftment and migration of human bone marrow stromal cells implanted in the brains of albino rats - Similarities to astrocyte grafts. Proc Natl Acad Sci 1998; 95(7): 3908-13.
[39]
Eglitis MA, Dawson D, Park KW, Mouradian MM. Targeting of marrow-derived astrocytes to the ischemic brain. Neuroreport 1999; 10(6): 1289-92.
[http://dx.doi.org/10.1097/00001756-199904260-00025] [PMID: 10363941]
[40]
Jendelová P, Herynek V, Urdzíková L, et al. Magnetic resonance tracking of transplanted bone marrow and embryonic stem cells labeled by iron oxide nanoparticles in rat brain and spinal cord. J Neurosci Res 2004; 76(2): 232-43.http://doi.wiley.com/10.1002/jnr.20041
[http://dx.doi.org/10.1002/jnr.20041] [PMID: 15048921]
[41]
Nivet E, Vignes M, Girard SD, et al. Engraftment of human nasal olfactory stem cells restores neuroplasticity in mice with hippocampal lesions. J Clin Invest 2011; 121(7): 2808.
[42]
Wang L, Li Y, Chen J, et al. Ischemic cerebral tissue and MCP-1 enhance rat bone marrow stromal cell migration in interface culture. Exp Hematol 2002; 30(7): 831-6.
[http://dx.doi.org/10.1016/S0301-472X(02)00829-9] [PMID: 12135683]
[43]
Girard SD, Virard I, Lacassagne E, et al. From Blood to lesioned brain: An in vitro study on migration mechanisms of human nasal olfactory stem cells. Stem Cells Int 2017; 2017: 1478606.
[http://dx.doi.org/10.1155/2017/1478606] [PMID: 28698717]
[44]
Ould YA, Sbai O, Baranger K, et al. Role of matrix metalloproteinases in migration and neurotrophic properties of nasal olfactory stem and ensheathing cells Cell Transplant 2013; 22(6): 993-1010.http://pubmed.ncbi.nlm.nih.gov/23043957/
[http://dx.doi.org/10.3727/096368912X657468] [PMID: 23043957]
[45]
Enomoto M. The future of bone marrow stromal cell transplantation for the treatment of spinal cord injury Neural Regen Res 2015; 10(3): 383-4.https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4396098/
[http://dx.doi.org/10.4103/1673-5374.153684] [PMID: 25878584]
[46]
Haack SM, Bindslev L, Mortensen S, Friis T, Kastrup J. The influence of freezing and storage on the characteristics and functions of human mesenchymal stromal cells isolated for clinical use. Cytotherapy 2007; 9(4): 328-37.
[http://dx.doi.org/10.1080/14653240701322235] [PMID: 17573608]
[47]
Mueller SM, Glowacki J. Age-related decline in the osteogenic potential of human bone marrow cells cultured in threedimensional collagen sponges. J Cell Biochem 2001; 82(4): 583-90.http://onlinelibrary.wiley.com/doi/full/10.1002/jcb.1174
[http://dx.doi.org/10.1002/jcb.1174] [PMID: 11500936]
[48]
Oñate B, Vilahur G, Ferrer LR, et al. The subcutaneous adipose tissue reservoir of functionally active stem cells is reduced in obese patients. FASEB J 2012; 26(10): 4327-36.www.fasebj.org
[http://dx.doi.org/10.1096/fj.12-207217] [PMID: 22772162]
[49]
Nakano M, Fujimiya M. Potential effects of mesenchymal stem cell derived extracellular vesicles and exosomal miRNAs in neurological disorders. Neural Regen Res 2021; 16(12): 2359-66.http://pubmed.ncbi.nlm.nih.gov/33907007/
[http://dx.doi.org/10.4103/1673-5374.313026] [PMID: 33907007]
[50]
Nasirishargh A, Kumar P, Ramasubramanian L, et al. Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection. World J Stem Cells 2021; 13(7): 776-94.
[http://dx.doi.org/10.4252/wjsc.v13.i7.776] [PMID: 34367477]
[51]
Hernández R, Jiménez LC, Perales AJ, Perazzoli G, Melguizo C, Prados J. Differentiation of human mesenchymal stem cells towards neuronal lineage: Clinical trials in nervous system disorders. Biomol Ther Korean Society of Appl Pharmacol 2020; 28: 34-44.
[52]
Chopp M, Li Y. Treatment of neural injury with marrow stromal cells. Lancet Neurol 2002; 1(2): 92-100.http://linkinghub.elsevier.com/retrieve/pii/S1474442202000406
[http://dx.doi.org/10.1016/S1474-4422(02)00040-6] [PMID: 12849513]
[53]
Li Y, Chopp M, Chen J, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab 2000; 20(9): 1311-9.http://journals.sagepub.com/doi/10.1097/00004647-200009000-00006
[http://dx.doi.org/10.1097/00004647-200009000-00006] [PMID: 10994853]
[54]
Zhao LR, Duan WM, Reyes M, Keene CD, Verfaillie CM, Low WC. Human bone marrow stem cells exhibit neural phenotypes and ameliorate neurological deficits after grafting into the ischemic brain of rats. Exp Neurol 2002; 174(1): 11-20.
[http://dx.doi.org/10.1006/exnr.2001.7853] [PMID: 11869029]
[55]
Li Y, Chen J, Zhang CL, et al. Gliosis and brain remodeling after treatment of stroke in rats with marrow stromal cells. Glia 2005; 49(3): 407-17.http://doi.wiley.com/10.1002/glia.20126
[http://dx.doi.org/10.1002/glia.20126] [PMID: 15540231]
[56]
Oshita J, Okazaki T, Mitsuhara T, et al. Early transplantation of human cranial bone-derived mesenchymal stem cells enhances functional recovery in ischemic stroke model rats. Neurol Med Chir 2020; 60(2): 83.
[http://dx.doi.org/10.2176/nmc.oa.2019-0186]
[57]
Hu J, Chang Y, Peng C, Huang S, Li G, Li H. Umbilical cord mesenchymal stem cells derived neurospheres promote long-term functional recovery but aggravate acute phase inflammation in experimental stroke. Neuroscience 2022; 480: 217-8.https://pubmed.ncbi.nlm.nih.gov/34762983/
[http://dx.doi.org/10.1016/j.neuroscience.2021.10.032] [PMID: 34762983]
[58]
Ryu B, Sekine H, Homma J, et al. Allogeneic adipose-derived mesenchymal stem cell sheet that produces neurological improvement with angiogenesis and neurogenesis in a rat stroke model. J Neurosurg 2019; 132(2): 442-55.https://pubmed.ncbi.nlm.nih.gov/30797215/
[http://dx.doi.org/10.3171/2018.11.JNS182331] [PMID: 30797215]
[59]
Deng J, Li M, Meng F, et al. 3D spheroids of human placentaderived mesenchymal stem cells attenuate spinal cord injury in mice. Cell Death Dis 2021; 12(12): 1096..https://pubmed.ncbi.nlm.nih.gov/34803160/
[http://dx.doi.org/10.1038/s41419-021-04398-w] [PMID: 34803160]
[60]
Levy ML, Crawford JR, Dib N, Verkh L, Tankovich N, Cramer SC. Phase I/II study of safety and preliminary efficacy of intravenous allogeneic mesenchymal stem cells in chronic stroke. Stroke 2019; 50(10): 2835-41.https://pubmed.ncbi.nlm.nih.gov/31495331/
[http://dx.doi.org/10.1161/STROKEAHA.119.026318] [PMID: 31495331]
[61]
Jaillard A, Hommel M, Moisan A, et al. Autologous mesenchymal stem cells improve motor recovery in subacute ischemic stroke: a randomized clinical trial. Transl Stroke Res 2020; 11(5): 910-23.
[http://dx.doi.org/10.1007/s12975-020-00787-z] [PMID: 32462427]
[62]
Lalu MM, Montroy J, Dowlatshahi D, et al. From the lab to patients: A systematic review and meta-analysis of mesenchymal stem cell therapy for stroke. Transl Stroke Res 2019; 11(3): 345-64.
[63]
Sweeney MD, Zhao Z, Montagne A, Nelson AR, Zlokovic BV. Blood-brain barrier: From physiology to disease and back. Physiol Rev 2019; 99(1): 21.
[64]
Xin Y, Gao J, Hu R, et al. Changes of immune parameters of T lymphocytes and macrophages in EAE mice after BM-MSCs transplantation. Immunol Lett 2020; 225: 66-73.
[http://dx.doi.org/10.1016/j.imlet.2020.05.005] [PMID: 32544469]
[65]
Long X, Olszewski M, Huang W, Kletzel M. Neural cell differentiation in vitro from adult human bone marrow mesenchymal stem cells. Stem Cells Dev 2005; 14(1): 65-9.https://www.liebertpub.com/doi/abs/10.1089/scd.2005.14.65
[http://dx.doi.org/10.1089/scd.2005.14.65] [PMID: 15725745]
[66]
Dezawa M, Takahashi I, Esaki M, Takano M, Sawada H. Sciatic nerve regeneration in rats induced by transplantation of in vitro differentiated bone-marrow stromal cells. Eur J Neurosci 2001; 14(11): 1771-6.https://onlinelibrary.wiley.com/doi/full/10.1046/j.0953-816x.2001.01814.x
[http://dx.doi.org/10.1046/j.0953-816x.2001.01814.x] [PMID: 11860471]
[67]
Peng J, Wang Y, Zhang L, et al. Human umbilical cord Wharton’s jelly-derived mesenchymal stem cells differentiate into a Schwann-cell phenotype and promote neurite outgrowth in vitro. Brain Res Bull 2011; 84(3): 235-43.
[http://dx.doi.org/10.1016/j.brainresbull.2010.12.013] [PMID: 21194558]
[68]
Barthelmes J, Tafferner N, Kurz J, et al. Induction of experimental autoimmune encephalomyelitis in mice and evaluation of the disease- dependent distribution of immune cells in various tissues. J Vis Exp 2016; 2016(111): e53933.http://www.jove.com/es/v/53933/la-induccin-de-la-encefalomielitis-autoinmune-experimental-en-ratones?language=Spanish
[http://dx.doi.org/10.3791/53933] [PMID: 27214391]
[69]
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.
[http://dx.doi.org/10.1002/glia.20841]
[70]
Luz CP, Kurte M, Bravo AJ, et al. Mesenchymal stem cells generate a CD4+CD25+Foxp3+ regulatory T cell population during the differentiation process of Th1 and Th17 cells. Stem Cell Res Ther 2013; 4(3): 65.
[71]
Duffy MM, Pindjakova J, Hanley SA, et al. Mesenchymal stem cell inhibition of T-helper 17 cell- differentiation is triggered by cellcell contact and mediated by prostaglandin E2 via the EP4 receptor. Eur J Immunol 2011; 41(10): 2840-51.http://onlinelibrary.wiley.com/doi/full/10.1002/eji.201141499
[http://dx.doi.org/10.1002/eji.201141499] [PMID: 21710489]
[72]
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): 753-61.https://jamanetwork.com/journals/jamaneurology/fullarticle/795748
[http://dx.doi.org/10.1001/archneur.65.6.753] [PMID: 18541795]
[73]
Zappia E, Casazza S, Pedemonte E, et al. Mesenchymal stem cells ameliorate experimental autoimmune encephalomyelitis inducing T-cell anergy. Blood 2005; 106(5): 1755-61.
[http://dx.doi.org/10.1182/blood-2005-04-1496] [PMID: 15905186]
[74]
Liu Y, Ma Y, Du B, Wang Y, Yang GY, Bi X. Mesenchymal stem cells attenuated blood-brain barrier disruption via downregulation of aquaporin-4 expression in eae mice. Mol Neurobiol 2020; 57(9): 3891.
[http://dx.doi.org/10.1007/s12035-020-01998-z]
[75]
Trubiani O, Giacoppo S, Ballerini P, et al. Alternative source of stem cells derived from human periodontal ligament: a new treatment for experimental autoimmune encephalomyelitis. Stem Cell Res Ther 2016; 7: 1.
[http://dx.doi.org/10.1186/s13287-015-0253-4]
[76]
Anderson P, Gonzalez RE, 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.
[77]
Bowles AC, Strong AL, Wise RM, et al. Adipose stromal vascular fraction-mediated improvements at late-stage disease in a murine model of multiple sclerosis. Stem Cells 2017; 35(2): 532-44.https://academic.oup.com/stmcls/article/35/2/532/6421135
[http://dx.doi.org/10.1002/stem.2516] [PMID: 27733015]
[78]
Ke F, Zhang L, Liu Z, et al. Soluble tumor necrosis factor receptor 1 released by skin-derived mesenchymal stem cells is critical for inhibiting th17 cell differentiation. Stem Cells Transl Med 2016; 5(3): 301-13.
[79]
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): 2077-98.https://journals.sagepub.com/doi/10.3727/096368914X685104?url_ver=Z39.88-2003&rfr_id=ori%3Arid%3Acrossref.org&rfr_dat=cr_pub++0pubmed
[http://dx.doi.org/10.3727/096368914X685104] [PMID: 25310756]
[80]
Shu J, He X, Li H, et al. The beneficial effect of human amnion mesenchymal cells in inhibition of inflammation and induction of neuronal repair in eae mice. J Immunol Res 2018; 2018: 5083797.
[81]
Freedman MS, Bar-Or A, Atkins HL, et al. The therapeutic potential of mesenchymal stem cell transplantation as a treatment for multiple sclerosis: consensus report of the International MSCT Study Group. Mult Scler 2010; 16(4): 503-10.http://journals.sagepub.com/doi/abs/10.1177/1352458509359727
[http://dx.doi.org/10.1177/1352458509359727] [PMID: 20086020]
[82]
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.
[83]
Sahraian MA, Mohyeddin Bonab M, Baghbanian SM, Owji M, Naser Moghadasi A. Therapeutic use of intrathecal mesenchymal stem cells in patients with multiple sclerosis: A pilot study with booster injection. Immunol Invest 2019; 48(2): 160-8.https://pubmed.ncbi.nlm.nih.gov/30156938/
[http://dx.doi.org/10.1080/08820139.2018.1504301] [PMID: 30156938]
[84]
Fernández O, 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.
[85]
Lu Z, Zhu L, Liu Z, Wu J, Xu Y, Zhang CJ. IV/IT hUC-MSCs Infusion in RRMS and NMO: A 10-Year follow-up study. Front Neurol 2020; 11: 967.
[86]
Karussis D, Karageorgiou C, Vaknin DA, 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.
[http://dx.doi.org/10.1001/archneurol.2010.248]
[87]
Mohajeri M, Farazmand A, Mohyeddin BM, Nikbin B, Minagar A. FOXP3 gene expression in multiple sclerosis patients pre- and post mesenchymal stem cell therapy. Iran J Allergy Asthma Immunol 2011; 10(3): 155-61.https://ijaai.tums.ac.ir/index.php/ijaai/article/view/306
[PMID: 21891821]
[88]
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.
[89]
Chopp M, Zhang XH, Li Y, et al. Spinal cord injury in rat: treatment with bone marrow stromal cell transplantation. Neuroreport 2000; 11(13): 3001-5.http://journals.lww.com/00001756-200009110-00035
[http://dx.doi.org/10.1097/00001756-200009110-00035] [PMID: 11006983]
[90]
Hofstetter CP, Schwarz EJ, Hess D, et al. Marrow stromal cells form guiding strands in the injured spinal cord and promote recovery. Proc Natl Acad Sci 2002; 99(4): 2199-04.
[http://dx.doi.org/10.1073/pnas.042678299]
[91]
Cízková D, Rosocha J, Vanický I, Jergová S, Cízek M. Transplants of human mesenchymal stem cells improve functional recovery after spinal cord injury in the rat. Cell Mol Neurobiol 2006; 26(7-8): 1167-80.http://link.springer.com/10.1007/s10571-006-9093-1
[http://dx.doi.org/10.1007/s10571-006-9093-1] [PMID: 16897366]
[92]
Sasaki M, Honmou O, Akiyama Y, Uede T, Hashi K, Kocsis JD. Transplantation of an acutely isolated bone marrow fraction repairs demyelinated adult rat spinal cord axons. Glia 2001; 35(1): 26-34.
[http://dx.doi.org/10.1002/glia.1067]
[93]
Akiyama Y, Radtke C, Kocsis JD. Remyelination of the rat spinal cord by transplantation of identified bone marrow stromal cells. J Neurosci 2002; 22(15): 6623-30.
[94]
Akiyama Y, Radtke C, Honmou O, Kocsis JD. Remyelination of the spinal cord following intravenous delivery of bone marrow cells. Glia 2002; 39(3): 229-36.
[http://dx.doi.org/10.1002/glia.10102]
[95]
Zhou X, Chu X, Yuan H, et al. Mesenchymal stem cell derived EVs mediate neuroprotection after spinal cord injury in rats via the microRNA-21-5p/FasL gene axis. Biomed Pharmacother 2019; 115: 108818.http://pubmed.ncbi.nlm.nih.gov/31102912/
[http://dx.doi.org/10.1016/j.biopha.2019.108818] [PMID: 31102912]
[96]
Boido M, Ghibaudi M, Gentile P, Favaro E, Fusaro R, Tonda TC. Chitosan-based hydrogel to support the paracrine activity of mesenchymal stem cells in spinal cord injury treatment. Sci Rep 2019; 9(1): 6402.https://pubmed.ncbi.nlm.nih.gov/31024032/
[http://dx.doi.org/10.1038/s41598-019-42848-w] [PMID: 31024032]
[97]
Albu S, Kumru H, Coll R, et al. Clinical effects of intrathecal administration of expanded Wharton jelly mesenchymal stromal cells in patients with chronic complete spinal cord injury: a randomized controlled study. Cytotherapy 2021; 23(2): 146-56.http://pubmed.ncbi.nlm.nih.gov/32981857/
[http://dx.doi.org/10.1016/j.jcyt.2020.08.008] [PMID: 32981857]
[98]
Cheng H, Liu X, Hua R, et al. Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury. J Transl Med 2014; 12(1): 253.https://pubmed.ncbi.nlm.nih.gov/25209445/
[http://dx.doi.org/10.1186/s12967-014-0253-7] [PMID: 25209445]
[99]
Dai G, Liu X, Zhang Z, Yang Z, Dai Y, Xu R. Transplantation of autologous bone marrow mesenchymal stem cells in the treatment of complete and chronic cervical spinal cord injury. Brain Res 2013; 1533: 73-9.
[http://dx.doi.org/10.1016/j.brainres.2013.08.016] [PMID: 23948102]
[100]
Liu S, Zhang H, Wang H, et al. A comparative study of different stem cell transplantation for spinal cord injury: a systematic review and network meta-analysis. World Neurosurg 2021. Available from:https://pubmed.ncbi.nlm.nih.gov/34954058/
[101]
Zurita M, Vaquero J. Functional recovery in chronic paraplegia after bone marrow stromal cells transplantation. Neuroreport 2004; 15(7): 1105-8.http://journals.lww.com/00001756-200405190-00004
[http://dx.doi.org/10.1097/00001756-200405190-00004] [PMID: 15129154]
[102]
Bhat IA, T B S , Somal A, et al. An allogenic therapeutic strategy for canine spinal cord injury using mesenchymal stem cells. J Cell Physiol 2019; 234(3): 2705-18.https://pubmed.ncbi.nlm.nih.gov/30132873/
[http://dx.doi.org/10.1002/jcp.27086] [PMID: 30132873]
[103]
Sharun K, Kumar R, Chandra V, et al. Percutaneous transplantation of allogenic bone marrow-derived mesenchymal stem cells for the management of paraplegia secondary to Hansen type I intervertebral disc herniation in a Beagle dog. Majallah-i Tahqiqat-i Dampizishki-i Iran 2021; 22(2): 161-6.https://pubmed.ncbi.nlm.nih.gov/34306116/
[PMID: 34306116]
[104]
Phedy P, Djaja YP, Gatam L, et al. Motoric recovery after transplantation of bone marrow derived mesenchymal stem cells in chronic spinal cord injury: A case report. Am J Case Rep 2019; 20: 1299-304.
[http://dx.doi.org/10.12659/AJCR.917624] [PMID: 31474745]
[105]
Samii A, Nutt JG, Ransom BR. Parkinson’s disease. Lancet 2004; 363(9423): 1783-93.
[106]
Li Y, Chen J, Wang L, Zhang L, Lu M, Chopp M. Intracerebral transplantation of bone marrow stromal cells in a 1-methyl-4- phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson’s disease. Neurosci Lett 2001; 316(2): 67-70.https://pubmed.ncbi.nlm.nih.gov/11742717/
[http://dx.doi.org/10.1016/S0304-3940(01)02384-9] [PMID: 11742717]
[107]
Wang YL, Liu XS, Wang SS, et al. Curcumin-activated mesenchymal stem cells derived from human umbilical cord and their effects on mptp-mouse model of parkinson’s disease: A new biological therapy for parkinson’s disease. Stem Cells Int 2020; 2020: 4636397.
[108]
Ghahari L, Safari M, Rahimi Jaberi K, Jafari B, Safari K, Madadian M. Mesenchymal stem cells with granulocyte colony-stimulating factor reduce stress oxidative factors in Parkinson’s disease. Iran Biomed J 2020; 24(2): 89-98.https://pubmed.ncbi.nlm.nih.gov/31677610/
[http://dx.doi.org/10.29252/ibj.24.2.89] [PMID: 31677610]
[109]
Li Q, Wang Z, Xing H, Wang Y, Guo Y. Exosomes derived from miR-188-3p-modified adipose-derived mesenchymal stem cells protect Parkinson’s disease. Mol Ther Nucleic Acids 2021; 23: 1334-44.https://pubmed.ncbi.nlm.nih.gov/33717653/
[http://dx.doi.org/10.1016/j.omtn.2021.01.022] [PMID: 33717653]
[110]
Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Prim 2015; 1(1): 1-18. [Epub Ahead of Print]
[http://dx.doi.org/10.1038/nrdp.2015.56]
[111]
Sterniczuk R, Antle MC, Laferla FM, Dyck RH. Characterization of the 3xTg-AD mouse model of Alzheimer’s disease: part 2. Behavioral and cognitive changes. Brain Res 2010; 1348: 149-55.http://pubmed.ncbi.nlm.nih.gov/20558146/
[http://dx.doi.org/10.1016/j.brainres.2010.06.011] [PMID: 20558146]
[112]
Park BN, Kim JH, Lim TS, et al. Therapeutic effect of mesenchymal stem cells in an animal model of Alzheimer’s disease evaluated by β-amyloid positron emission tomography imaging. Aust N Z J Psychiatry 2020; 54(9): 883-91.https://pubmed.ncbi.nlm.nih.gov/32436738/
[http://dx.doi.org/10.1177/0004867420917467] [PMID: 32436738]
[113]
Losurdo M, Pedrazzoli M, D’Agostino C, et al. Intranasal delivery of mesenchymal stem cell-derived extracellular vesicles exerts immunomodulatory and neuroprotective effects in a 3xTg model of Alzheimer’s disease. Stem Cells Transl Med 2020; 9(9): 1068-84.https://pubmed.ncbi.nlm.nih.gov/32496649/
[http://dx.doi.org/10.1002/sctm.19-0327] [PMID: 32496649]
[114]
Wang Y, Jiang J, Fu X, et al. Fe3O4 polydopamine nanoparticleloaded human umbilical cord mesenchymal stem cells improve the cognitive function in Alzheimer’s disease mice by promoting hippocampal neurogenesis. Nanomedicine 2022; 40: 102507.http://pubmed.ncbi.nlm.nih.gov/34883265/
[http://dx.doi.org/10.1016/j.nano.2021.102507] [PMID: 34883265]
[115]
Zaazaa AM, El-Motelp BAA, Ali NA, Youssef AM, Sayed MA, Mohamed SH. Stem cell-derived exosomes and copper sulfide nanoparticles attenuate the progression of neurodegenerative disorders induced by cadmium in rats. Heliyon 2022; 8(1): e08622.
[http://dx.doi.org/10.1016/j.heliyon.2021.e08622]
[116]
Bagheri MS. Stem cell-based therapy as a promising approach in Alzheimer’s disease: current perspectives on novel treatment. Cell Tissue Bank 2021; 22(3): 339-53.https://pubmed.ncbi.nlm.nih.gov/33398492/
[http://dx.doi.org/10.1007/s10561-020-09896-3] [PMID: 33398492]
[117]
Hernández AE, García E. Mesenchymal stem cell therapy for Alzheimer’s disease. Stem Cells Int 2021; 2021: 7834421.
[http://dx.doi.org/10.1155/2021/7834421]
[118]
Pacheco HM, Soto RLO, Reyes SH, et al. Current status and challenges of stem cell treatment for Alzheimer’s disease. J Alzheimers Dis 2021; 84(3): 917-35.https://pubmed.ncbi.nlm.nih.gov/34633316/
[http://dx.doi.org/10.3233/JAD-200863] [PMID: 34633316]
[119]
Guo L, Wei X, Jiang P. The use of gene-modified bone marrow mesenchymal stem cells for cochlear cell therapy. Transpl Immunol 2021; 68: 101433.https://pubmed.ncbi.nlm.nih.gov/34197926/
[http://dx.doi.org/10.1016/j.trim.2021.101433] [PMID: 34197926]
[120]
Tsai SCS, Yang KD, Chang KH, et al. Umbilical cord mesenchymal stromal cell-derived exosomes rescue the loss of outer hair cells and repair cochlear damage in cisplatin-injected mice. Int J Mol Sci 2021; 22(13): 6664.https://pubmed.ncbi.nlm.nih.gov/34206364/
[http://dx.doi.org/10.3390/ijms22136664] [PMID: 34206364]
[121]
Chen J, Li Y, Katakowski M, et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res 2003; 73(6): 778-86.http://doi.wiley.com/10.1002/jnr.10691
[http://dx.doi.org/10.1002/jnr.10691] [PMID: 12949903]
[122]
Bao X, Wei J, Feng M, et al. Transplantation of human bone marrow-derived mesenchymal stem cells promotes behavioral recovery and endogenous neurogenesis after cerebral ischemia in rats. Brain Res 2011; 1367: 103-3.https://pubmed.ncbi.nlm.nih.gov/20977892/
[http://dx.doi.org/10.1016/j.brainres.2010.10.063] [PMID: 20977892]
[123]
Gerdoni E, Gallo B, Casazza S, et al. Mesenchymal stem cells effectively modulate pathogenic immune response in experimental autoimmune encephalomyelitis. Ann Neurol 2007; 61(3): 219-7.http://doi.wiley.com/10.1002/ana.21076
[http://dx.doi.org/10.1002/ana.21076] [PMID: 17387730]
[124]
Lu Z, Hu X, Zhu C, Wang D, Zheng X, Liu Q. Overexpression of CNTF in mesenchymal stem cells reduces demyelination and induces clinical recovery in experimental autoimmune encephalomyelitis mice. J Neuroimmunol 2009; 206(1-2): 58-69.http://pubmed.ncbi.nlm.nih.gov/19081144/
[http://dx.doi.org/10.1016/j.jneuroim.2008.10.014] [PMID: 19081144]
[125]
Gordon D, Pavlovska G, Uney JB, Wraith DC, Scolding NJ. Human mesenchymal stem cells infiltrate the spinal cord, reduce demyelination, and localize to white matter lesions in experimental autoimmune encephalomyelitis. J Neuropathol Exp Neurol 2010; 69(11): 1087-95.https://academic.oup.com/jnen/article-lookup/doi/10.1097/NEN.0b013e3181f97392
[http://dx.doi.org/10.1097/NEN.0b013e3181f97392] [PMID: 20940628]
[126]
Chung HJ, Chung WH, Lee JH, et al. Expression of neurotrophic factors in injured spinal cord after transplantation of human-umbilical cord blood stem cells in rats. J Vet Sci 2016; 17(1): 97-102.
[127]
Gu C, Li H, Wang C, et al. Bone marrow mesenchymal stem cells decrease CHOP expression and neuronal apoptosis after spinal cord injury. Neurosci Lett 2017; 636: 282-9.
[http://dx.doi.org/10.1016/j.neulet.2016.11.032] [PMID: 27865878]
[128]
Melo FR, Bressan RB, Forner S, et al. Transplantation of human skin-derived mesenchymal stromal cells improves locomotor recovery after spinal cord injury in rats. Cell Mol Neurobiol 2017; 37(5): 941-7.https://link.springer.com/article/10.1007/s10571-016-0414-8
[http://dx.doi.org/10.1007/s10571-016-0414-8] [PMID: 27510317]
[129]
Levy YS, Bahat SM, Barzilay R, et al. Regenerative effect of neural-induced human mesenchymal stromal cells in rat models of Parkinson’s disease. Cytotherapy 2008; 10(4): 340-52.
[http://dx.doi.org/10.1080/14653240802021330] [PMID: 18574767]
[130]
Bahat SM, Barhum Y, Levy YS, et al. Induction of adult human bone marrow mesenchymal stromal cells into functional astrocytelike cells: potential for restorative treatment in Parkinson’s disease. J Mol Neurosci 2009; 39(1-2): 199-210.https://pubmed.ncbi.nlm.nih.gov/19127447/
[http://dx.doi.org/10.1007/s12031-008-9166-3] [PMID: 19127447]
[131]
Blandini F, Cova L, Armentero MT, et al. Transplantation of undifferentiated human mesenchymal stem cells protects against 6-hydroxydopamine neurotoxicity in the rat. Cell Transplant 2010; 19(2): 203-17.http://journals.sagepub.com/doi/full/10.3727/096368909X479839
[http://dx.doi.org/10.3727/096368909X479839] [PMID: 19906332]
[132]
Xiong N, Cao X, Zhang Z, et al. Long-term efficacy and safety of human umbilical cord mesenchymal stromal cells in rotenoneinduced hemiparkinsonian rats. Biol Blood Marrow Transplant 2010; 16(11): 1519-29.http://www.tctjournal.org/article/S1083879110002454/fulltext
[http://dx.doi.org/10.1016/j.bbmt.2010.06.004] [PMID: 20542126]
[133]
Salama M, Sobh M, Emam M, et al. Effect of intranasal stem cell administration on the nigrostriatal system in a mouse model of Parkinson’s disease. Exp Ther Med 2017; 13(3): 976-82.
[http://dx.doi.org/10.3892/etm.2017.4073]
[134]
Boika A, Aleinikava N, Chyzhyk V, Zafranskaya M, Nizheharodava D, Ponomarev V. Mesenchymal stem cells in Parkinson’s disease: Motor and nonmotor symptoms in the early posttransplant period. Surg Neurol Int 2020; 11: 380.
[http://dx.doi.org/10.25259/SNI_233_2020] [PMID: 33408914]
[135]
Kamiya K, Fujinami Y, Hoya N, et al. Mesenchymal stem cell transplantation accelerates hearing recovery through the repair of injured cochlear fibrocytes. Am J Pathol 2007; 171(1): 214-6.
[http://dx.doi.org/10.2353/ajpath.2007.060948]
[136]
Cho YB, Cho HH, Jang S, Jeong HS, Park JS. Transplantation of neural differentiated human mesenchymal stem cells into the cochlea of an auditory-neuropathy guinea pig model. J Korean Med Sci 2011; 26(4): 492-8.
[137]
Pandit SR, Sullivan JM, Egger V, Borecki AA, Oleskevich S. Functional effects of adult human olfactory stem cells on earlyonset sensorineural hearing loss. Stem Cells 2011; 29(4): 670-7.http://doi.wiley.com/10.1002/stem.609
[http://dx.doi.org/10.1002/stem.609] [PMID: 21312317]
[138]
Zhou Y, Yuan J, Zhou B, et al. The therapeutic efficacy of human adipose tissue-derived mesenchymal stem cells on experimental autoimmune hearing loss in mice. Immunology 2011; 133(1): 133-40.
[http://dx.doi.org/10.1111/j.1365-2567.2011.03421.x]
[139]
Choi MY, Yeo SW, Park KH. Hearing restoration in a deaf animal model with intravenous transplantation of mesenchymal stem cells derived from human umbilical cord blood. Biochem Biophys Res Commun 2012; 427(3): 629-36.
[http://dx.doi.org/10.1016/j.bbrc.2012.09.111] [PMID: 23026045]
[140]
Kil K, Choi MY, Kong JS, Kim WJ, Park KH. Regenerative efficacy of mesenchymal stromal cells from human placenta in sensorineural hearing loss. Int J Pediatr Otorhinolaryngol 2016; 91: 72-81.
[http://dx.doi.org/10.1016/j.ijporl.2016.10.010] [PMID: 27863646]
[141]
Ma Y, Guo W, Yi H, et al. Transplantation of human umbilical cord mesenchymal stem cells in cochlea to repair sensorineural hearing. Am J Transl Res 2016; 8(12): 5235-45.www.ajtr.org
[PMID: 28077998]