Multipl skleroz ve bilişsel bozuklukta çok hedefli farmasötik ilaçları test etmek için beyın organoidi modelinin geliştirilmesi ve beyin organoidi oluşturulması için alternatif ekstraselüler matrisin incelenmesi

Brain organoids offer a valuable platform for modeling immune-mediated neurodegenerative disorders. Multiple sclerosis (MS), characterized by CNS-targeted autoimmunity, neuroinflammation, and demyelination, lacks robust in vitro models and effective therapies. To address this, MS-modelled brain organoids were developed using commercial extracellular matrix (Matrigel) and GelMA; LPS treatment induced MS pathology, and fingolimod derivatives were evaluated for therapeutic potential on the organoids. The results were analyzed by light microscopy, immunofluorescent microscopy, Raman spectroscopy, qRT-PCR, and ELISA. It was found that GelMA is effective as Matrigel to generate brain organoids with diverse neuron types (astrocytes, neural progenitor cells, mature neurons) but different spatially organized cell population, MS can be modelled with LPS induction, causing decreased myelination (2.4-fold in CNPase expression) and increased inflammation (1.7-fold in IBA1, 1.6-fold for GFAP, 4.4-fold NF-κB and 6.7-fold for IL-6 expression) on brain organoids, and at least one of the compounds, ST-1505 would be a promising drug candidate because it increases myelination (2.9-fold MBP expression), decreases the inflammation (2.6-fold GFAP, 4-fold TNF-α, 2.3-fold FOXP3, 2.5-fold CSF-1 expression) and decreases the expression of cognitive impairment related markers (1.9-fold TAU expression).