Dibutyryl Cyclic AMP Inhibits the Progression of Experimental Autoimmune Encephalomyelitis and Potentiates Recruitment of Endogenous Neural Stem Cells

2013 ◽  
Vol 51 (2) ◽  
pp. 298-306 ◽  
Author(s):  
Shiva Khezri ◽  
Mohammad Javan ◽  
Mahdi Goudarzvand ◽  
Saeed Semnanian ◽  
Hossein Baharvand
Keyword(s):  
Stem Cells ◽  
Cyclic Amp ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neural Stem Cells ◽  
Dibutyryl Cyclic Amp ◽  
Autoimmune Encephalomyelitis ◽  
Endogenous Neural Stem Cells ◽  
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 Comparative Effects of Human Neural Stem Cells and Oligodendrocyte Progenitor Cells on the Neurobehavioral Disorders of Experimental Autoimmune Encephalomyelitis Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Dae-Kwon Bae ◽  
Dongsun Park ◽  
Sun Hee Lee ◽  
Goeun Yang ◽  
Jangbeen Kyung ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Neural Stem Cells ◽  
Neurotrophic Factor ◽  
Demyelinating Diseases ◽  
Autoimmune Response ◽  
Autoimmune Encephalomyelitis ◽  
Human Neural Stem Cells ◽  
Experimental Autoimmune

Since multiple sclerosis (MS) is featured with widespread demyelination caused by autoimmune response, we investigated the recovery effects of F3.olig2 progenitors, established by transducing human neural stem cells (F3 NSCs) with Olig2 transcription factor, in myelin oligodendrocyte glycoprotein- (MOG-) induced experimental autoimmune encephalomyelitis (EAE) model mice. Six days after EAE induction, F3 or F3.olig2 cells (1 × 106/mouse) were intravenously transplanted. MOG-injected mice displayed severe neurobehavioral deficits which were remarkably attenuated and restored by cell transplantation, in which F3.olig2 cells were superior to its parental F3 cells. Transplanted cells migrated to the injured spinal cord, matured to oligodendrocytes, and produced myelin basic proteins (MBP). The F3.olig2 cells expressed growth and neurotrophic factors including brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), ciliary neurotrophic factor (CNTF), and leukemia inhibitory factor (LIF). In addition, the transplanted cells markedly attenuated inflammatory cell infiltration, reduced cytokine levels in the spinal cord and lymph nodes, and protected host myelins. The results indicate that F3.olig2 cells restore neurobehavioral symptoms of EAE mice by regulating autoimmune inflammatory responses as well as by stimulating remyelination and that F3.olig2 progenitors could be a candidate for the cell therapy of demyelinating diseases including MS.

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