Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis

被引:0
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作者
Perussolo, Maiara Carolina [1 ]
Mogharbel, Bassam Felipe [1 ]
Sacaki, Claudia Sayuri [1 ]
da Rosa, Nadia Nascimento [1 ]
Irioda, Ana Carolina [1 ]
de Oliveira, Nathalia Barth [1 ]
Appel, Julia Maurer [1 ]
Luhrs, Larissa [1 ]
Meira, Leanderson Franco [2 ]
Guarita-Souza, Luiz Cesar [2 ]
Nagashima, Seigo [3 ]
de Paula, Caroline Busatta Vaz [3 ]
Noronha, Lucia de [3 ]
Zotarelli-Filho, Idiberto Jose [4 ]
Abdelwahid, Eltyeb [5 ]
de Carvalho, Katherine Athayde Teixeira [1 ]
机构
[1] Child & Adolescent Hlth Res & Pequeno Principe Fac, Pele Pequeno Principe Res Inst, Adv Therapy & Cellular Biotechnol Regenerat Med De, POB 80240-020, BR-80240020 Curitiba, Parana, Brazil
[2] Pontif Catholic Univ Parana, Inst Biol & Hlth Sci, Expt Lab, POB 80215-901, Curitiba, Parana, Brazil
[3] Pontif Catholic Univ Parana PUCPR, Sch Med, Grad Program Hlth Sci, Lab Expt Pathol, POB 80215-901, Curitiba, Parana, Brazil
[4] Sao Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci IBILCE, Postgrad Program Food Nutr & Food Engn, POB 15054-000, Sao Jose Do Rio Preto, SP, Brazil
[5] Northwestern Univ, Feinberg Cardiovasc Res Inst, Feinberg Sch Med, Chicago, IL 60611 USA
关键词
human; Wharton's jelly; mesenchymal stem cells; neural precursors; cellular therapy; experimental autoimmune encephalomyelitis; immunomodulatory; neuroprotection; multiple sclerosis; translation; STEM-CELLS; MODELS; MSCS; EAE;
D O I
10.3390/ijms25136996
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
This study aims to evaluate and compare cellular therapy with human Wharton's jelly (WJ) mesenchymal stem cells (MSCs) and neural precursors (NPs) in experimental autoimmune encephalomyelitis (EAE), a preclinical model of Multiple Sclerosis. MSCs were isolated from WJ by an explant technique, differentiated to NPs, and characterized by cytometry and immunocytochemistry analysis after ethical approval. Forty-eight rats were EAE-induced by myelin basic protein and Freund's complete adjuvant. Forty-eight hours later, the animals received intraperitoneal injections of 250 ng/dose of Bordetella pertussis toxin. Fourteen days later, the animals were divided into the following groups: a. non-induced, induced: b. Sham, c. WJ-MSCs, d. NPs, and e. WJ-MSCs plus NPs. 1 x 10(5). Moreover, the cells were placed in a 10 mu L solution and injected via a stereotaxic intracerebral ventricular injection. After ten days, the histopathological analysis for H&E, Luxol, interleukins, and CD4/CD8 was carried out. Statistical analyses demonstrated a higher frequency of clinical manifestation in the Sham group (15.66%) than in the other groups; less demyelination was seen in the treated groups than the Sham group (WJ-MSCs, p = 0.016; NPs, p = 0.010; WJ-MSCs + NPs, p = 0.000), and a lower cellular death rate was seen in the treated groups compared with the Sham group. A CD4/CD8 ratio of <1 showed no association with microglial activation (p = 0.366), astrocytes (p = 0.247), and cell death (p = 0.577) in WJ-MSCs. WJ-MSCs and NPs were immunomodulatory and neuroprotective in cellular therapy, which would be translated as an adjunct in demyelinating diseases.
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页数:21
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