ArticleOsteoarthritis and cartilage open2025
Development of an iPSC-based screening platform identifying enhancers of chondrogenesis.
Article in Osteoarthritis and cartilage open, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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8 authors.
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Abstract
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 % O 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.
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