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Myelin Oligodendrocyte Glycoprotein MOG35-55 Induced Experimental Autoimmune Encephalomyelitis EAE in C57BL/6 Mice
Published on: April 15, 2014
Genetically Engineered Artificial Microvesicles Carrying Nerve Growth Factor Restrains the Progression of Autoimmune
Reem Alatrash1, Maria Golubenko1, Ekaterina Martynova1
1Institute of Fundamental Medicine and Biology, Kazan (Volga Region) Federal University, 420008 Kazan, Russia.
Abstract:
Multiple sclerosis (MS) is an incurable, progressive chronic autoimmune demyelinating disease. Therapy for MS is based on slowing down the processes of neurodegeneration and suppressing the immune system of patients. MS is accompanied by inflammation, axon-degeneration and neurogliosis in the central nervous system. One of the directions for a new effective treatment for MS is cellular, subcellular, as well as gene therapy. We investigated the therapeutic potential of adipose mesenchymal stem cell (ADMSC) derived, cytochalasin B induced artificial microvesicles (MVs) expressing nerve growth factor (NGF) on a mouse model of multiple sclerosis experimental autoimmune encephalomyelitis (EAE). These ADMSC-MVs-NGF were tested using histological, immunocytochemical and molecular genetic methods after being injected into the tail vein of animals on the 14th and 21st days post EAE induction. ADMSC-MVs-NGF contained the target protein inside the cytoplasm. Their injection into the caudal vein led to a significant decrease in neurogliosis at the 14th and 21st days post EAE induction. Artificial ADMSC-MVs-NGF stimulate axon regeneration and can modulate gliosis in the EAE model.
Insights
Artificial microvesicles derived from adipose mesenchymal stem cells and engineered to express nerve growth factor show therapeutic potential. These ADMSC-MVs-NGF significantly reduced neurogliosis in a mouse model of multiple sclerosis.
Area of Science:
- Neuroscience
- Immunology
- Regenerative Medicine
Background:
- Multiple sclerosis (MS) is a chronic autoimmune disease causing neurodegeneration and neuroinflammation.
- Current MS therapies focus on immune suppression and slowing disease progression.
- Novel therapeutic strategies, including cell and gene therapy, are needed for MS.
Purpose of the Study:
- To investigate the therapeutic efficacy of engineered adipose mesenchymal stem cell-derived microvesicles (ADMSC-MVs) expressing nerve growth factor (NGF) in a mouse model of MS.
- To evaluate the impact of ADMSC-MVs-NGF on neuroinflammation and axon regeneration.
Main Methods:
- Experimental autoimmune encephalomyelitis (EAE) mouse model induced for MS.
- Intravenous injection of ADMSC-MVs-NGF on days 14 and 21 post-induction.
- Histological, immunocytochemical, and molecular genetic analyses to assess therapeutic effects.
Main Results:
- ADMSC-MVs-NGF were successfully generated and contained functional NGF.
- Significant reduction in neurogliosis observed at 14 and 21 days post-EAE induction.
- Evidence of stimulated axon regeneration and modulated gliosis in the EAE model.
Conclusions:
- Engineered ADMSC-MVs-NGF demonstrate significant therapeutic potential for MS.
- This approach may offer a novel strategy for promoting axon regeneration and managing neuroinflammation in MS.
- Further research into cell-free therapy using engineered microvesicles is warranted.
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