scholarly journals Neural Stem Cells Reversed Disease Symptoms in an Experimental Autoimmune Encephalomyelitis Mouse Model of Multiple Sclerosis

2021 ◽  
Author(s):  
Christina Brown ◽  
Christina McKee ◽  
Sophia Halassy ◽  
Suleiman Kojan ◽  
Douglas L. Feinstein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neural Stem Cells ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune Encephalomyelitis Mouse ◽  
Disease Symptoms ◽  
Experimental Autoimmune

scholarly journals Neural stem cells reversed disease symptoms in an experimental autoimmune encephalomyelitis mouse model of multiple sclerosis

2021 ◽  
Author(s):  
Christina Brown ◽  
Christina McKee ◽  
Sophia Halassy ◽  
Suleiman Kojan ◽  
Douglas Feinstein ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Stem Cells ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neural Stem Cells ◽  
Cell Transplantation ◽  
Blue Staining ◽  
Autoimmune Encephalomyelitis ◽  
Disease Symptoms ◽  
Experimental Autoimmune

Abstract Background Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system (CNS). MS affects millions of people and causes a great economic and societal burden. Currently used treatment drugs have side effects and only address the symptoms but not the causes of MS. In this study, a novel approach of transplanting neural stem cells (NSCs) derived from human primitive mesenchymal stem cells (MSCs) was investigated in an experimental autoimmune encephalomyelitis (EAE) mouse model of MS. Methods Primitive MSCs were differentiated into NSCs using selective media. The cells were labeled with PKH26 and injected into the tail vein of EAE mice. The animals were evaluated for changes in neurobehavior and weight twice daily. Two weeks following cell transplantation, the animals were sacrificed to collect the blood, lymphatic and CNS tissues for analysis. FACS analysis was used to track labeled cells and infiltrates. Histochemical analysis was performed to determine the levels of myelination. Expression of inflammation, neural, astrogliosis, neuroprotection, and myelination markers was investigated by using immunohistochemical and qRT-PCR analyses. Results Neurobehavioral assays showed that EAE disease process was halted by transplantation of both MSCs and NSCs. However, NSCs showed greater efficacy in reversing the disease symptoms, which resulted in near complete recovery of EAE animals. Post-transplantation analyses also showed homing of transplanted cells into the CNS with concomitant induction of anti-inflammatory response resulting in reduction of immune infiltrates. Luxol fast blue staining intensity of CNS tissues was significantly improved in treated mice as compared to EAE animals, suggesting endogenous remyelination. NSC transplantation also modulated Treg and Th17 cells in EAE mice to levels comparable to healthy controls. In addition, several of the markers associated with neuroprotection (i.e. Igf, Bdnf, and Trkb), myelination (i.e. Erk2, Krox-20, Oct-6, Mpz, Mbp, and Mog) and neurogenesis (i.e. Tuj1 and Nestin) were upregulated, suggesting endogenous regeneration in treated animals. Conclusions Cell transplantation was more effective at an earlier point of EAE disease (EAE stage 1) than later (EAE stage 2). These promising results provide basis for large-scale clinical studies to treat MS using NSCs derived from primitive MSCs.

scholarly journals The S100B Inhibitor Pentamidine Ameliorates Clinical Score and Neuropathology of Relapsing—Remitting Multiple Sclerosis Mouse Model

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 748 ◽  
Author(s):  
Gabriele Di Sante ◽  
Susanna Amadio ◽  
Beatrice Sampaolese ◽  
Maria Elisabetta Clementi ◽  
Mariagrazia Valentini ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Clinical Score ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune Encephalomyelitis Mouse ◽  
Extracellular Signaling ◽  
Relapsing Remitting ◽  
Inflammatory Processes ◽  
Experimental Autoimmune

S100B is an astrocytic protein acting either as an intracellular regulator or an extracellular signaling molecule. A direct correlation between increased amount of S100B and demyelination and inflammatory processes has been demonstrated. The aim of this study is to investigate the possible role of a small molecule able to bind and inhibit S100B, pentamidine, in the modulation of disease progression in the relapsing–remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the central nervous system, we observed that pentamidine is able to delay the acute phase of the disease and to inhibit remission, resulting in an amelioration of clinical score when compared with untreated relapsing–remitting experimental autoimmune encephalomyelitis mice. Moreover, we observed a significant reduction of proinflammatory cytokines expression levels in the brains of treated versus untreated mice, in addition to a reduction of nitric oxide synthase activity. Immunohistochemistry confirmed that the inhibition of S100B was able to modify the neuropathology of the disease, reducing immune infiltrates and partially protecting the brain from the damage. Overall, our results indicate that pentamidine targeting the S100B protein is a novel potential drug to be considered for multiple sclerosis treatment.

scholarly journals S100B Protein as a Therapeutic Target in Multiple Sclerosis: The S100B Inhibitor Arundic Acid Protects from Chronic Experimental Autoimmune Encephalomyelitis

2021 ◽  
Vol 22 (24) ◽  
pp. 13558
Author(s):  
Chiara Camponeschi ◽  
Maria De Carluccio ◽  
Susanna Amadio ◽  
Maria Elisabetta Clementi ◽  
Beatrice Sampaolese ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Mouse Model ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Disease Onset ◽  
Treated Group ◽  
S100b Protein ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune Encephalomyelitis Mouse ◽  
Clinical Scores ◽  
Experimental Autoimmune

S100B is an astrocytic protein behaving at high concentration as a damage-associated molecular pattern molecule. A direct correlation between the increased amount of S100B and inflammatory processes has been demonstrated, and in particular, the inhibitor of S100B activity pentamidine has been shown to ameliorate clinical scores and neuropathologic-biomolecular parameters in the relapsing-remitting experimental autoimmune encephalomyelitis mouse model of multiple sclerosis. This study investigates the effect of arundic acid (AA), a known inhibitor of astrocytic S100B synthesis, in the chronic experimental autoimmune encephalomyelitis, which is another mouse model of multiple sclerosis usually studied. By the daily evaluation of clinical scores and neuropathologic-molecular analysis performed in the spinal cord, we observed that the AA-treated group showed lower severity compared to the vehicle-treated mice, particularly in the early phase of disease onset. We also observed a significant reduction of astrocytosis, demyelination, immune infiltrates, proinflammatory cytokines expression and enzymatic oxidative reactivity in the AA-treated group. Overall, our results reinforce the involvement of S100B in the development of animal models of multiple sclerosis and propose AA targeting the S100B protein as a focused potential drug to be considered for multiple sclerosis treatment.

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