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Transplantation of human umbilical cord mesenchymal stem cells optimized with IFN-γ is a potential procedure for modification of motor impairment in multiple sclerosis cases: a preclinical systematic review and meta-analysis study

  • Received : 2024.03.28
  • Accepted : 2024.05.14
  • Published : 2024.09.30

Abstract

Stem cells transplantation (SCT) is known as a newfound strategy for multiple sclerosis (MS) treatment. Human umbilical cord mesenchymal stem cells (hUCMSCs) contain various regenerative features. Experimental autoimmune encephalomyelitis (EAE) is a laboratory model of MS. This meta-analysis study was conducted to assess the overall therapeutic effects of hUCMSCs on reduction of clinical score (CS) and restoration of active movement in EAE-induced animals. For comprehensive searching (in various English and Persian databases until May 1, 2024), the main keywords of "Experimental Autoimmune Encephalomyelitis", "Multiple Sclerosis", "Human", "Umbilical Cord", "Mesenchymal", and "Stem Cell" were hired. Collected data were transferred to the citation manager software (EndNote x8) and duplicate papers were merged. Primary and secondary screenings were applied (according to the inclusion and exclusion criteria) and eligible studies were prepared for data collection. CS of two phases of peak and recovery of EAE were extracted as the difference in means and various analyses including heterogeneity, publication bias, funnel plot, and sensitivity index were reported. Meta-analysis was applied by CMA software (v.2), P<0.05 was considered a significant level, and the confidence interval (CI) was determined 95% (95% CI). Six eligible high-quality (approved by ARRIVE checklist) papers were gathered. The difference in means of peak and recovery phases were -0.775 (-1.325 to -0.225; P=0.006; I2=90.417%) and -1.230 (-1.759 to -0.700; P<0.001; I2=93.402%), respectively. The overall therapeutic effects of SCT of hUCMSCs on the EAE cases was -1.011 (95% CI=-1.392 to -0.629; P=0.001). hUCMSCs transplantation through the intravenous route to the animal MS model (EAE) seems a considerably effective procedure for the alleviation of motor defects in both phases of peak and recovery.

Keywords

Acknowledgement

This study was approved by Baqiyatallah University of Medical Sciences (401000213) and this university was the responsible funding provision.

References

  1. Perez-Jeldres T, Alvarez-Lobos M, Rivera-Nieves J. Targeting sphingosine-1-phosphate signaling in immune-mediated diseases: beyond multiple sclerosis. Drugs 2021;81:985-1002.  https://doi.org/10.1007/s40265-021-01528-8
  2. Walton C, King R, Rechtman L, Kaye W, Leray E, Marrie RA, Robertson N, La Rocca N, Uitdehaag B, van der Mei I, Wallin M, Helme A, Angood Napier C, Rijke N, Baneke P. Rising prevalence of multiple sclerosis worldwide: insights from the Atlas of MS, third edition. Mult Scler 2020;26:1816-21.  https://doi.org/10.1177/1352458520970841
  3. Constantinescu CS, Farooqi N, O'Brien K, Gran B. Experimental autoimmune encephalomyelitis (EAE) as a model for multiple sclerosis (MS). Br J Pharmacol 2011;164:1079-106.  https://doi.org/10.1111/j.1476-5381.2011.01302.x
  4. Yamanaka S. Pluripotent stem cell-based cell therapy-promise and challenges. Cell Stem Cell 2020;27:523-31.  https://doi.org/10.1016/j.stem.2020.09.014
  5. Brignier AC, Gewirtz AM. Embryonic and adult stem cell therapy. J Allergy Clin Immunol 2010;125(2 Suppl 2):S336-44.  https://doi.org/10.1016/j.jaci.2009.09.032
  6. Alatyyat SM, Alasmari HM, Aleid OA, Abdel-Maksoud MS, Elsherbiny N. Umbilical cord stem cells: background, processing and applications. Tissue Cell 2020;65:101351. 
  7. Kim JY, Jeon HB, Yang YS, Oh W, Chang JW. Application of human umbilical cord blood-derived mesenchymal stem cells in disease models. World J Stem Cells 2010;2:34-8.  https://doi.org/10.4252/wjsc.v2.i2.34
  8. Yaghoubi Y, Movassaghpour A, Zamani M, Talebi M, Mehdizadeh A, Yousefi M. Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment. Life Sci 2019;233:116733. 
  9. Liu R, Zhang Z, Lu Z, Borlongan C, Pan J, Chen J, Qian L, Liu Z, Zhu L, Zhang J, Xu Y. Human umbilical cord stem cells ameliorate experimental autoimmune encephalomyelitis by regulating immunoinflammation and remyelination. Stem Cells Dev 2013;22:1053-62.  https://doi.org/10.1089/scd.2012.0463
  10. 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;69:1087-95.  https://doi.org/10.1097/NEN.0b013e3181f97392
  11. Liu S, Wang J, Han R, Meng M, Wang W, Zhao Y, Yang F, Yang L, Gao H, Zhao Y, Yang L, Wang R, Tang W, Li Y, Duan S, Wang J, He Z, Li L, Hou Z. Therapeutic effect of transplanted umbilical cord mesenchymal stem cells in a cynomolgus monkey model of multiple sclerosis. Am J Transl Res 2019;11:2516-31. 
  12. Subirana M, Sola I, Garcia JM, Gich I, Urrutia G. A nursing qualitative systematic review required MEDLINE and CINAHL for study identification. J Clin Epidemiol 2005;58:20-5.  https://doi.org/10.1016/j.jclinepi.2004.06.001
  13. Percie du Sert N, Hurst V, Ahluwalia A, Alam S, Avey MT, Baker M, Browne WJ, Clark A, Cuthill IC, Dirnagl U, Emerson M, Garner P, Holgate ST, Howells DW, Karp NA, Lazic SE, Lidster K, MacCallum CJ, Macleod M, Pearl EJ, Petersen OH, Rawle F, Reynolds P, Rooney K, Sena ES, Silberberg SD, Steckler T, Wurbel H. The ARRIVE guidelines 2.0: updated guidelines for reporting animal research. J Cereb Blood Flow Metab 2020;40:1769-77.  https://doi.org/10.1177/0271678X20943823
  14. Abdolmaleki A, Kondori BJ, Raei M, Ghaleh HEG. Cell therapy procedure using anti-inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: a preclinical systematic review and meta-analysis study. Fundam Clin Pharmacol 2023;37:215-25.  https://doi.org/10.1111/fcp.12844
  15. Ahmadvand Koohsari S, Absalan A, Azadi D. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles attenuate experimental autoimmune encephalomyelitis via regulating pro and anti-inflammatory cytokines. Sci Rep 2021;11:11658. 
  16. Zhou X, Liu X, Liu L, Han C, Xie Z, Liu X, Xu Y, Li F, Bi J, Zheng C. Transplantation of IFN-γ primed hUCMSCs significantly improved outcomes of experimental autoimmune encephalomyelitis in a mouse model. Neurochem Res 2020;45:1510-7.  https://doi.org/10.1007/s11064-020-03009-y
  17. Torkaman M, Ghollasi M, Mohammadnia-Afrouzi M, Salimi A, Amari A. The effect of transplanted human Wharton's jelly mesenchymal stem cells treated with IFN-γ on experimental autoimmune encephalomyelitis mice. Cell Immunol 2017;311:1-12.  https://doi.org/10.1016/j.cellimm.2016.09.012
  18. Donders R, Vanheusden M, Bogie JF, Ravanidis S, Thewissen K, Stinissen P, Gyselaers W, Hendriks JJ, Hellings N. Human Wharton's jelly-derived stem cells display immunomodulatory properties and transiently improve rat experimental autoimmune encephalomyelitis. Cell Transplant 2015;24:2077-98.  https://doi.org/10.3727/096368914X685104
  19. Mikaeili Agah E, Parivar K, Joghataei MT. Therapeutic effect of transplanted human Wharton's jelly stem cell-derived oligodendrocyte progenitor cells (hWJ-MSC-derived OPCs) in an animal model of multiple sclerosis. Mol Neurobiol 2014;49:625-32.  https://doi.org/10.1007/s12035-013-8543-2
  20. Bai L, Shao H, Wang H, Zhang Z, Su C, Dong L, Yu B, Chen X, Li X, Zhang X. Effects of mesenchymal stem cell-derived exosomes on experimental autoimmune uveitis. Sci Rep 2017;7:4323. 
  21. Amari A, Ebtekar M, Moazzeni SM, Soleimani M, Amirabad LM, Tahoori MT, Massumi M. Investigation of immunomodulatory properties of human Wharton's Jelly-derived mesenchymal stem cells after lentiviral transduction. Cell Immunol 2015;293:59-66.  https://doi.org/10.1016/j.cellimm.2014.12.003
  22. Zhong XY, Zhang B, Asadollahi R, Low SH, Holzgreve W. Umbilical cord blood stem cells: what to expect. Ann N Y Acad Sci 2010;1205:17-22.  https://doi.org/10.1111/j.1749-6632.2010.05659.x
  23. Gasiuniene M, Valatkaite E, Navakauskiene R. Long-term cultivation of human amniotic fluid stem cells: the impact on proliferative capacity and differentiation potential. J Cell Biochem 2020;121:3491-501.  https://doi.org/10.1002/jcb.29623
  24. Wang L, Wang J, Zhou X, Sun J, Zhu B, Duan C, Chen P, Guo X, Zhang T, Guo H. A new self-healing hydrogel containing hucMSC-derived exosomes promotes bone regeneration. Front Bioeng Biotechnol 2020;8:564731. 
  25. Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther 2020;11:492. 
  26. Latifpour M, Shakiba Y, Amidi F, Mazaheri Z, Sobhani A. Differentiation of human umbilical cord matrix-derived mesenchymal stem cells into germ-like cells. Avicenna J Med Biotechnol 2014;6:218-27. 
  27. Chen K, Wang D, Du WT, Han ZB, Ren H, Chi Y, Yang SG, Zhu D, Bayard F, Han ZC. Human umbilical cord mesenchymal stem cells hUC-MSCs exert immunosuppressive activities through a PGE2-dependent mechanism. Clin Immunol 2010;135:448-58.  https://doi.org/10.1016/j.clim.2010.01.015
  28. Yun JW, Ahn JH, Kwon E, Kim SH, Kim H, Jang JJ, Kim WH, Kim JH, Han SY, Kim JT, Kim JH, Kim W, Ku SY, Do BR, Kang BC. Human umbilical cord-derived mesenchymal stem cells in acute liver injury: hepatoprotective efficacy, subchronic toxicity, tumorigenicity, and biodistribution. Regul Toxicol Pharmacol 2016;81:437-47.  https://doi.org/10.1016/j.yrtph.2016.09.029
  29. Na L, Wang S, Liu T, Zhang L. Ultrashort wave combined with human umbilical cord mesenchymal stem cell (HUC-MSC) transplantation inhibits NLRP3 inflammasome and improves spinal cord injury via MK2/TTP signalling pathway. Biomed Res Int 2020;2020:3021750. 
  30. Feng YW, Wu C, Liang FY, Lin T, Li WQ, Jing YH, Dai P, Yu HX, Lan Y, Pei Z, Xu GQ. hUCMSCs mitigate LPS-induced trained immunity in ischemic stroke. Front Immunol 2020;11:1746. 
  31. Jiang Z, Wang J, Sun G, Feng M. BDNF-modified human umbilical cord mesenchymal stem cells-derived dopaminergic-like neurons improve rotation behavior of Parkinson's disease rats through neuroprotection and anti-neuroinflammation. Mol Cell Neurosci 2022;123:103784. 
  32. Ahmed SO, El Fakih R, Elhaddad A, Hamidieh AA, Altbakhi A, Chaudhry QU, Bazarbachi A, Adil S, Al-Khabori M, Ben Othman T, Gaziev J, Khalaf M, Alshammeri S, Alotaibi S, Alshahrani M, Bekadja MA, Ibrahim A, Al-Wahadneh AM, Altarshi M, Alsaeed A, Madani A, Abboud M, Abujazar H, Bakr M, Abosoudah I, El Cheikh J, Almasari A, Alfraih F, Baldomero H, Elsolh H, Niederwieser D, Chaudhri N, Aljurf M. Strategic priorities for hematopoietic stem cell transplantation in the EMRO region. Hematol Oncol Stem Cell Ther 2023;16:162-9.  https://doi.org/10.1016/j.hemonc.2021.09.006
  33. Sterner RC, Sterner RM. CAR-T cell therapy: current limitations and potential strategies. Blood Cancer J 2021;11:69. 
  34. Rohaan MW, Borch TH, van den Berg JH, Met O, Kessels R, Geukes Foppen MH, Stoltenborg Granhoj J, Nuijen B, Nijenhuis C, Jedema I, van Zon M, Scheij S, Beijnen JH, Hansen M, Voermans C, Noringriis IM, Monberg TJ, Holmstroem RB, Wever LDV, van Dijk M, Grijpink-Ongering LG, Valkenet LHM, Torres Acosta A, Karger M, Borgers JSW, Ten Ham RMT, Retel VP, van Harten WH, Lalezari F, van Tinteren H, van der Veldt AAM, Hospers GAP, Stevense-den Boer MAM, Suijkerbuijk KPM, Aarts MJB, Piersma D, van den Eertwegh AJM, de Groot JB, Vreugdenhil G, Kapiteijn E, Boers-Sonderen MJ, Fiets WE, van den Berkmortel FWPJ, Ellebaek E, Holmich LR, van Akkooi ACJ, van Houdt WJ, Wouters MWJM, van Thienen JV, Blank CU, Meerveld-Eggink A, Klobuch S, Wilgenhof S, Schumacher TN, Donia M, Svane IM, Haanen JBAG. Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma. N Engl J Med 2022;387:2113-25.  https://doi.org/10.1056/NEJMoa2210233
  35. Hoang DM, Pham PT, Bach TQ, Ngo ATL, Nguyen QT, Phan TTK, Nguyen GH, Le PTT, Hoang VT, Forsyth NR, Heke M, Nguyen LT. Stem cell-based therapy for human diseases. Signal Transduct Target Ther 2022;7:272. 
  36. Ma D, Xu K, Zhang G, Liu Y, Gao J, Tian M, Wei C, Li J, Zhang L. Immunomodulatory effect of human umbilical cord mesenchymal stem cells on T lymphocytes in rheumatoid arthritis. Int Immunopharmacol 2019;74:105687. 
  37. Remya NS, Nair PD. Mechanoresponsiveness of human umbilical cord mesenchymal stem cells in in vitro chondrogenesis-a comparative study with growth factor induction. J Biomed Mater Res A 2016;104:2554-66.  https://doi.org/10.1002/jbm.a.35792
  38. Gao X, He GH, Zhang XT, Chen S. Protective effect of human umbilical cord mesenchymal stem cell-derived exosomes on rat retinal neurons in hyperglycemia through the brain-derived neurotrophic factor/TrkB pathway. Int J Ophthalmol 2021;14:1683-9.  https://doi.org/10.18240/ijo.2021.11.06
  39. Liao Z, Yang X, Wang W, Deng W, Zhang Y, Song A, Ni B, Zhao H, Zhang S, Li Z. hucMSCs transplantation promotes locomotor function recovery, reduces apoptosis and inhibits demyelination after SCI in rats. Neuropeptides 2021;86:102125.