Extracellular Vesicle Treatment Alleviates Neurodevelopmental and Neurodegenerative Pathology in Cortical Spheroid Model of Down Syndrome
Year: 2023
Type: article
Abstract: Down syndrome (DS), or trisomy 21, is manifested in a variety of anatomical and cellular abnormalities resulting in intellectual deficits and early onset of Alzheimer's disease (AD) with no effective treatments available to alleviate the pathologies associated with the disorder. The therapeutic potential of extracellular vesicles (EVs) has emerged recently in relation to various neurological conditions. We have previously demonstrated the therapeutic efficacy of mesenchymal stromal cell-derived EVs (MSC-EVs) in cellular and functional recovery in a rhesus monkey model of cortical injury. In the current study, we evaluated the therapeutic effect of MSC-EVs in a cortical spheroid (CS) model of DS generated from patient-derived induced pluripotent stem cells (iPSCs). Compared to euploid controls, trisomic CS display smaller size, deficient neurogenesis, and AD-related pathological features, such as enhanced cell death and depositions of amyloid beta (Aβ) and hyperphosphorylated tau (p-tau). EV-treated trisomic CS demonstrated preserved size, partial rescue in the production of neurons, significantly decreased levels of Aβ and p-tau, and a reduction in the extent of cell death as compared to the untreated trisomic CS. Together, these results show the efficacy of EVs in mitigating DS and AD-related cellular phenotypes and pathological depositions in human CS.
DOI: 10.3390/ijms24043477
Institutions: Boston University, University of Massachusetts Amherst
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,780
Awards: Neural substrates of exosome-mediated enhancement of recovery after cortical injury in non-human primates., Exosomes from bone marrow-derived mesenchymal stem cells as a restorative treatment in a non-human primate model of cerebral injury, Studying Epigenetic Dysregulation in Down Syndrome Using Fluorescent Reporter Cell Lines, G5375835812, G5469392656, G7874994702, Epigenetic Determinants in Oligodendrocyte Maturation in Down Syndrome, Extracellular Vesicle treatment and age-related neuropathology in non-human primates, Development of myelinating oligodendrocytes in Down syndrome, G9000202519, Extracellular Vesicle treatment and age-related neuropathology in non-human primates, Mechanisms underlying extracellular vesicle mediated changes in inflammation, neural circuitry and plasticity following cortical injury in aged monkeys
OpenAlex ID: W4319983412