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BMSCs-Derived Extracellular VesiclemiR-29a-3p Improved the Stability of Rat Myasthenia Gravis by Regulating Treg/Th17
Zhongben Tang1, Meiqiu Chen2, Chen Chen1
1Department of Thoracic, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Introduction:
Myasthenia gravis (MG) is an autoimmune disorder. Microvesicle-derived miRNAs have been implicated in autoimmune diseases. However, the role of microvesicle-derived miR-29a-3p in MG remains poorly understood. This study aimed to investigate the therapeutic effect and mechanism of miR-29a-3p derived from stem cell microvesicles (MVs) on experimental autoimmune myasthenia gravis (EAMG) rats.
Methods:
EAMG was induced in rats by injection of the subunit of the rat nicotinic anti-acetylcholine receptor (AChR) R97-116 peptide.Besides the control group, EAMG rats were randomly allocated into the EAMG model group, MV group, MV-NC-agomir group, and MV- miR-29a-3p-agomir group.
Results:
Our results found that BMSCs-MV promoted miR-29a-3p expression in gastrocnemius of EAMG rats. Bone marrow mesenchymal stem cells (BMSCs) derived microvesicle miR-29a-3p improved the hanging ability and swimming time of EMGA rats and weakened the degree of muscle fiber atrophy. Furthermore, microvesicles from miR-29a-3p overexpressing BMSCs reduced the content of AchR-Ab in the serum of EAMG rats. BMSC-derived microvesicle miR-29a-3p further suppressed the expression of IFN-γ and enhanced the IL-4 and IL-10 in the serum of EAMG rats by restoring the Th17/Treg cells balance.
Discussion:
BMSCs-derived microvesicle miR-29a-3p improved the stability of rat myasthenia gravis by regulating Treg/Th17 cells. It may be an effective treatment for MG.
Insights
Microvesicle miR-29a-3p from stem cells shows therapeutic potential for myasthenia gravis (MG). This treatment improved muscle function and immune balance in rats with experimental autoimmune MG (EAMG).
Area of Science:
- Immunology
- Molecular Biology
- Neuroscience
Background:
- Myasthenia gravis (MG) is an autoimmune disease affecting neuromuscular junctions.
- Microvesicle-derived microRNAs (miRNAs) are implicated in autoimmune disorders.
- The specific role of miR-29a-3p in MG pathogenesis is not well understood.
Purpose of the Study:
- To investigate the therapeutic effects of miR-29a-3p delivered via stem cell-derived microvesicles (MVs) in a rat model of experimental autoimmune myasthenia gravis (EAMG).
- To elucidate the underlying mechanism of miR-29a-3p action in EAMG.
Main Methods:
- EAMG was induced in rats using a nicotinic acetylcholine receptor peptide.
- Rats were treated with MVs, control MVs, or MVs engineered to overexpress miR-29a-3p (MV-miR-29a-3p-agomir).
- Assessments included motor function tests, muscle histology, serum antibody levels, and immune cell profiling (Th17/Treg balance).
Main Results:
- Bone marrow mesenchymal stem cell (BMSC)-derived MVs promoted miR-29a-3p expression in EAMG rats.
- Treatment with BMSC-derived miR-29a-3p MVs improved motor function (hanging and swimming) and reduced muscle atrophy.
- These MVs decreased anti-acetylcholine receptor antibodies (AchR-Ab), suppressed IFN-γ, and enhanced IL-4 and IL-10 by restoring Treg/Th17 balance.
Conclusions:
- BMSC-derived microvesicle miR-29a-3p demonstrates significant therapeutic benefits in an EAMG rat model.
- The mechanism involves modulating the Treg/Th17 cell balance, suggesting a potential novel treatment strategy for myasthenia gravis.
