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Войти в исследования Osteoarthritis and cartilage open · 2025
Development of an iPSC-based screening platform identifying enhancers of chondrogenesis.
СтатьяНазвание и аннотация: Перевод в очереди
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O'Brien Aisling, Xu Maojia, O'Connell Enda, Morrison Aline M, Shaw Georgina, Dutton James R, Murphy Mary, Barry Frank
Аннотация
OBJECTIVE: There is currently no long-term treatment for the repair of damaged cartilage and osteoarthritis (OA). Induced pluripotent stem cells (iPSCs) are an ideal cell source for screening platforms due to their ability to self-renew and differentiate to cell types that would otherwise require invasive surgeries to obtain, such as chondrocytes and mesenchymal stromal cells (MSCs). Here, we developed an iPSC-based screening platform and tested previously described pro-chondrogenic small molecule compounds, to determine their potential to identify hits.
DESIGN: iPSC derived chondroprogenitors (iCPs) and neural crest cell (NCC) derived MSCs (iNCC-MSCs) were generated, and their chondrogenic potential was confirmed. The iPSC derived cells and a primary bone marrow derived MSC (BM-MSC) line were cultured as pellets and treated with different concentrations of small molecule compounds, in the presence of chondrogenic inducing growth factors, over 14 days at 2 % O2. Glycosaminoglycan (GAG) synthesis was quantified by a 1,9- dimethylmethylene blue (DMMB) assay.
RESULTS: After 14 days of chondrogenesis, forskolin, baicalin and sesamin enhanced GAG synthesis in the iCPs, and forskolin enhanced GAG synthesis in the iNCC-MSCs, while no small molecule compounds enhanced GAG synthesis in the BM-MSCs.
CONCLUSION: Our findings further demonstrate how the small molecules pro-chondrogenic effects are dependent on the screening platform conditions, including the cell type, molecule concentration, 3D culture, hypoxia, and the inclusion of additional growth factors. The iPSC-based screening platform developed has the potential to identify disease modifying OA drugs (DMOADs) in novel compound screening libraries.
DESIGN: iPSC derived chondroprogenitors (iCPs) and neural crest cell (NCC) derived MSCs (iNCC-MSCs) were generated, and their chondrogenic potential was confirmed. The iPSC derived cells and a primary bone marrow derived MSC (BM-MSC) line were cultured as pellets and treated with different concentrations of small molecule compounds, in the presence of chondrogenic inducing growth factors, over 14 days at 2 % O2. Glycosaminoglycan (GAG) synthesis was quantified by a 1,9- dimethylmethylene blue (DMMB) assay.
RESULTS: After 14 days of chondrogenesis, forskolin, baicalin and sesamin enhanced GAG synthesis in the iCPs, and forskolin enhanced GAG synthesis in the iNCC-MSCs, while no small molecule compounds enhanced GAG synthesis in the BM-MSCs.
CONCLUSION: Our findings further demonstrate how the small molecules pro-chondrogenic effects are dependent on the screening platform conditions, including the cell type, molecule concentration, 3D culture, hypoxia, and the inclusion of additional growth factors. The iPSC-based screening platform developed has the potential to identify disease modifying OA drugs (DMOADs) in novel compound screening libraries.