{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,8]],"date-time":"2025-11-08T22:59:37Z","timestamp":1762642777274,"version":"3.40.5"},"reference-count":30,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100005849","name":"Baqiyatallah University of Medical Sciences","doi-asserted-by":"publisher","award":["400000308"],"award-info":[{"award-number":["400000308"]}],"id":[{"id":"10.13039\/501100005849","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Macrophage M2 (MP2)\u2010based cell therapy is a novel medicinal treatment for animals with Experimental Autoimmune Encephalomyelitis (EAE) as an experimental model of multiple sclerosis (MS). This systematic review and meta\u2010analysis study was designed to assess the overall therapeutic effects of MP2 cell therapy on <jats:italic>Clinical Score<\/jats:italic> and motor impairment in EAE\u2010induced animals. All experiments on MP2 cell therapy in animals with EAE were gathered (by October 2, 2022) from English (PubMed, Scopus, WoS, Science Direct, and ISC) and Persian (MagIran and SID) databases. The searching strategy was designed using \u201c<jats:italic>Experimental Autoimmune Encephalomyelitis<\/jats:italic>,\u201d \u201c<jats:italic>Multiple Sclerosis<\/jats:italic>,\u201d and \u201c<jats:italic>Macrophage M2<\/jats:italic>\u201d keywords. Following primary and secondary screenings, eligible papers were selected based on the PRISMA 2020 guideline, and the study quality was assessed using the Animal Research: Reporting of In Vivo Experiments (ARRIVE) checklist. The difference in means of <jats:italic>Clinical Score<\/jats:italic> (score 0\u20135) as the effect size (ES) was analyzed based on the random effect model (CMA software, v.2). Subgrouping (EAE phases of Onset, Peak, and Recovery) was applied, and <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup> index was used to assess the heterogeneity index. Publication bias and sensitivity indices were also evaluated. <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.05 was considered significant, and the confidence interval (CI) was determined 95%. Among 22 gathered papers, medium to high quality studies were selected for meta\u2010analysis. Difference in means, <jats:italic>P<\/jats:italic> value, and <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup> for Onset, Peak, and Recovery phases were 0.082 (CI95%: \u22120.323\u20130.159, <jats:italic>P<\/jats:italic> value: 0.504, <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>: 67.961%), \u22120.606 (CI95%: \u22121.518 to \u22120.305, <jats:italic>P<\/jats:italic> value: 0.192, <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>: 96.070%), and \u22121.103 (CI95%: \u22121.390\u2009to\u2009\u22120.816, <jats:italic>P<\/jats:italic> value: 0.000, <jats:italic>I<\/jats:italic><jats:sup><jats:italic>2<\/jats:italic><\/jats:sup>: 30.880%), respectively and Overall Effect was found \u22120.509 (CI95%: \u22120.689\u2009to\u2009\u22120.328, <jats:italic>P<\/jats:italic> value\u2009&lt;\u20090.001). Also, <jats:italic>P<\/jats:italic> value (two\u2010tailed) indices for publication bias were 0.366 and 0.583 for Egger's regression intercept and Begg rank correlation, respectively. The <jats:italic>P<\/jats:italic> value for sensitivity was detected 0.003. Cell therapy procedure using MP2 can potentially alleviate the <jats:italic>Clinical Scores<\/jats:italic> Index and correct the motor defects in Recovery phase of EAE animals. In healthy mice, the brain and myelin surrounding neurons are in a healthy and physiological state (1). To evaluate MS in humans, it is necessary to model this type of disease in animals using EAE procedure through subcutaneous injection of CFA, MOG<jats:sub>35\u201355<\/jats:sub>, MT, and Pert. Thus, inflammation and autoimmunity occur, which finally lead to myelin destruction and motor symptoms (2). By aspiration of progenitor cells available in bone marrow, the MP2 can be isolated and cultured. By activation of these types of cells, a rich collection of MP2 can be prepared for the cell\u2010therapy process (3). After injection through the tail vein or intra\u2010peritoneal procedure, these cells can be located in CNS through crossing from the BBB. They begin their anti\u2010inflammatory activities and help repair the damaged myelin (4). Eventually, the clinical symptoms can be modified considerably, and the animal motor function improves (5). CFA, complete Freund's adjuvant; MOG<jats:sub>35\u201355<\/jats:sub>, myelin oligodendrocyte glycoprotein; MT, <jats:italic>M<jats:styled-content style=\"fixed-case\">ycobacterium tuberculosis<\/jats:styled-content><\/jats:italic>; Pert, pertussis; EAE, Experimental Autoimmune Encephalomyelitis; BM, bone marrow; MP2, macrophage M2; and BBB, blood brain barrier.<\/jats:p>","DOI":"10.1111\/fcp.12844","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T10:24:49Z","timestamp":1666866289000},"page":"215-225","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Cell therapy procedure using anti\u2010inflammatory macrophage M2 can potentially reduce Clinical Score in animals with Experimental Autoimmune Encephalomyelitis: A preclinical systematic review and meta\u2010analysis study"],"prefix":"10.1111","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9541-8829","authenticated-orcid":false,"given":"Amir","family":"Abdolmaleki","sequence":"first","affiliation":[{"name":"Department of Anatomical Sciences, Medical School Baqiyatallah University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahman Jalali","family":"Kondori","sequence":"additional","affiliation":[{"name":"Department of Anatomical Sciences, Faculty of Medicine Baqiyatallah University of Medical Sciences  Tehran Iran"},{"name":"Baqiyatallah Research Center for Gastroenterology and Liver Diseases (BRCGL) Baqiyatallah University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehdi","family":"Raei","sequence":"additional","affiliation":[{"name":"Health Research Center, Life Style Institute Baqiyatallah University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hadi Esmaeili Gouvarchin","family":"Ghaleh","sequence":"additional","affiliation":[{"name":"Applied Virology Research Center, Medical School Baqiyatallah University of Medical Sciences  Tehran Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573\u2010019\u20100035\u20102"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458520970841"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24224"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hbm.25247"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurol.2018.03.006"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020.173090"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2018.08.030"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1201\/9781315533247"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jclinepi.2004.06.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X20943823"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/cei.13572"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/glia.22643"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1177\/1352458510379243"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/icb.2008.99"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.07.031"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.042"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727\u201049\u201013625"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/0008\u20108749(84)90228\u20104"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.85.1.117"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.168.8.4173"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000294325.63006.f8"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2014.00514"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1631\/jzus.B1700003"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20101635"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/sji.12162"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2012.07.005"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep30696"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673\u20105374.233448"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.2174\/1567201817666200122163251"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.15283\/ijsc.2014.7.1.1"}],"container-title":["Fundamental &amp; 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