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Synergistic promotion of bone regeneration through co-culture of endothelial cells with mesenchymal stem cells in endochondral ossification organoids
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DOI：10.1186/s13287-025-04733-4.png)
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Abstract
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Endochondral ossification (ECO) is essential for bone regeneration, involving cartilage formation, hypertrophy, angiogenesis, and ossification. Co-culturing mesenchymal stem cells (MSCs) with endothelial cells (ECs) shows potential to enhance bone regeneration but has not been effectively applied to ECO strategy. We examined the synergistic effects of MSCs and ECs on chondrogenesis, osteogenesis, and angiogenesis, followed by transcriptomic analysis. ECO organoids were formed in the scaffolds, and a critical-sized calvarial bone defect model was used for in vivo evaluation. Co-culture of ECs and MSCs promoted osteogenic differentiation and hypertrophic chondrogenic differentiation of MSCs. The ECO organoids exhibited enhanced vascularization and improved mineralization. In vivo, the co-culture group showed superior vascularization and bone repair compared to the MSCs-only group. Co-culturing ECs with MSCs in ECO organoids enhances bone regeneration, offering a promising alternative to traditional tissue engineering strategies. This approach may improve therapeutic outcomes by promoting endochondral bone formation.
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