Cellular Therapy in Experimental Autoimmune Encephalomyelitis as an Adjuvant Treatment to Translate for Multiple Sclerosis.
Maiara Carolina PerussoloBassam Felipe MogharbelCláudia Sayuri SaçakiNádia Nascimento da RosaAna Carolina IriodaNathalia Barth de OliveiraJulia Maurer AppelLarissa LührsLeanderson Franco MeiraLuiz César Guarita-SouzaSeigo NagashimaCaroline Busatta Vaz de PaulaAnna Flávia Ribeiro Dos Santos MiggiolaroIdiberto José Zotarelli-FilhoEltyeb AbdelwahidKatherine Athayde Teixeira de CarvalhoPublished in: International journal of molecular sciences (2024)
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 × 10 5 . Moreover, the cells were placed in a 10 µL 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.
Keyphrases
- mesenchymal stem cells
- umbilical cord
- multiple sclerosis
- cell therapy
- bone marrow
- oxide nanoparticles
- cell death
- early stage
- induced apoptosis
- endothelial cells
- heart failure
- escherichia coli
- high glucose
- cell cycle arrest
- white matter
- drug induced
- clinical trial
- inflammatory response
- spinal cord injury
- left ventricular
- blood brain barrier
- oxidative stress
- induced pluripotent stem cells
- decision making
- endoplasmic reticulum stress
- atrial fibrillation
- binding protein
- neuropathic pain
- lipopolysaccharide induced
- platelet rich plasma
- pi k akt