Perhaps most people have heard of autism, and what might come to mind for some is the “astonishing memory” of a genius, but for many, it may be the image of “a child playing alone, not interacting with their surroundings, people, or objects, appearing very quiet, not speaking, moving awkwardly, exhibiting strange postures and behaviors, and ignoring others as if they were deaf, no matter how much they are called.”
Autism Spectrum Disorder (ASD), also known as autism spectrum disorder, is a neurodevelopmental disorder characterized primarily by difficulties in social communication and restricted, repetitive interests and behaviors. Whether it is deficiencies in social interaction, abnormal communication abilities, narrow interests and stereotyped behaviors, sensitivity to sensory input, or varying levels of intelligence, these traits exist on a continuum from mild to severe, from low to high!
According to United Nations data, over 70 million people globally are currently affected by autism.
Autism is a widespread developmental disorder that severely jeopardizes children’s physical and mental health, with an unclear etiology and a lack of effective therapeutic drugs, posing a significant public health challenge in today’s world.
In May 2024, a team led by Liang Shuang/Wu Lijie from the School of Public Health at Harbin Medical University published a high-level article titled “Synergistic effect of mesenchymal stem cell-derived extracellular vesicle and miR-137 alleviates autism-like behaviors by modulating the NF-κB pathway” in the Journal of Translational Medicine (Top journal, IF=7.4)(2024 May 13;22(1):446).
MicroRNA (miRNA) represents an important class of small regulatory RNAs that control gene expression post-transcriptionally by targeting mRNA for degradation or translation repression. Early studies have indicated that miRNAs play complex roles in major biological processes such as development, differentiation, growth, and metabolism. Particularly, due to the key role of miR-137 in brain function and its presumed involvement in the etiology of neuropsychiatric disorders and cancer, it has garnered significant interest. Research indicates that the development, differentiation, and maturation of the nervous system are closely related to the expression of miR-137 and its regulation of numerous downstream target genes across various pathways. In the largest genome-wide association studies, dysregulation of this molecule has also been linked to major psychiatric disorders through its position in highly associated schizophrenia variant alleles.
The research found that miR-137 neural-specific knockout mice exhibited typical ASD-like behaviors, including reduced social abilities, stereotyped repetitive behaviors, and learning and memory deficits. Moreover, mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) not only have functions in regulating cellular immunity, tissue regeneration, and repair but their unique nanostructure enables them to cross the blood-brain barrier, making them prominent in the treatment of neuropsychiatric disorders in recent years.
In this study, researchers initially detected significantly reduced levels of miR-137 in blood samples from ASD patients and brain tissues of the autism model BTBR mice. They explored the mechanism of action of mesenchymal stem cell-derived extracellular vesicles loaded with miR-137 (MSC-miR137-EVs) in improving ASD-like behaviors and alleviating neuroinflammation through in vivo and in vitro experiments. The results showed that MSC-EVs rich in miR-146a-5p and engineered MSC-miR137-EVs exerted immune regulatory functions by targeting the NF-κB signaling pathway, alleviating neuroinflammatory responses and neuronal apoptosis, thus significantly improving mouse social deficits, anxiety levels, and spatial learning and memory deficits associated with ASD-like behaviors. These research findings are expected to provide new strategies and theoretical basis for the treatment of ASD.
