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Background <p>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.</p> Methods <p>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.</p> Results <p>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.</p> Conclusions <p>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.</p>

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Synergistic promotion of bone regeneration through co-culture of endothelial cells with mesenchymal stem cells in endochondral ossification organoids

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月18日

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  • Yiqi Su,
  • Zihao He,
  • Jiaojiao Li,
  • Qianqian Chen,
  • Du Wang,
  • Zhen Yang,
  • Ye Yuan,
  • Long Chen,
  • Fanhao Ye,
  • Dan Xing,
  • Hui Li,
  • Jianhao Lin

摘要

Background

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.

Methods

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.

Results

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.

Conclusions

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.