Rejuvenation of tendon stem/progenitor cells for functional tendon regeneration through platelet-derived exosomes loaded with recombinant Yap1

通过载有重组 Yap1 的血小板衍生外泌体恢复肌腱干细胞/祖细胞的活力,以实现功能性肌腱再生

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作者:Jinwei Lu, Xiaohui Yang, Chaofan He, Yazhou Chen, Congsun Li, Sihao Li, Yuewei Chen, Yifan Wu, Zhihui Xiang, Jiawei Kang, Guangyao Jiang, Cong Wang, Mohamed Diaty Diarra, Rongxin He, Gang Feng, Ruijian Yan

Significance

This is the first study to explore that the hippo pathway downstream effector Yap is involved in tendon aging and repair processes, and is associated with the regenerative capabilities of TSPCs. In this syudy, Platelet-derived exosomes (PLT-Exos) act as an appropriate carrier platform for the delivery of recombinant Yap1 into TSPCs to regulate Yap activity. Effective Yap1 delivery inhibit oxidative stress-induced senescence associated phenotype of TSPCs by blocking ROS-mediated NF-κb signaling pathway activation. This study emphasizes that combined application of biomimetic scaffolds and Yap1 loaded PLT-Exos can provide structural support and promote rejuvenation of resident cells to assist functional regeneration for Achilles tendon defect, and has the prospect of clinical setting.

Statement of significance

This is the first study to explore that the hippo pathway downstream effector Yap is involved in tendon aging and repair processes, and is associated with the regenerative capabilities of TSPCs. In this syudy, Platelet-derived exosomes (PLT-Exos) act as an appropriate carrier platform for the delivery of recombinant Yap1 into TSPCs to regulate Yap activity. Effective Yap1 delivery inhibit oxidative stress-induced senescence associated phenotype of TSPCs by blocking ROS-mediated NF-κb signaling pathway activation. This study emphasizes that combined application of biomimetic scaffolds and Yap1 loaded PLT-Exos can provide structural support and promote rejuvenation of resident cells to assist functional regeneration for Achilles tendon defect, and has the prospect of clinical setting.

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