Cordycepin-Loaded Dental Pulp Stem Cell-Derived Exosomes Promote Aged Bone Repair by Rejuvenating Senescent Mesenchymal Stem Cells and Endothelial Cells.

Yu Wang, Shanshan Jin, Yaru Guo, Lisha Zhu, Yilong Lu, Jing Li, Boon Chin Heng, Yan Liu, Xuliang Deng

Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology &National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, China.Department of Orthodontics, Peking University School and Hospital of Stomatology & National Center for Stomatology &National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology, Beijing, 100081, China. · pubmed

Paper

Abstract

Aging impairs bone marrow mesenchymal stem cell (BMSC) functions as well as associated angiogenesis which is critical for bone regeneration and repair. Hence, repairing bone defects in elderly patients poses a formidable challenge in regenerative medicine. Here, the engineered dental pulp stem cell-derived exosomes loaded with the natural derivative of adenosine Cordycepin (CY@D-exos) are fabricated by means of the intermittent ultrasonic shock, which dually rejuvenates both senescent BMSCs and endothelial cells and significantly improve bone regeneration and repair in aged animals. CY@D-exos can efficiently overcome the senescence of aged BMSCs and enhance their osteogenic differentiation by activating NRF2 signaling and maintaining heterochromatin stability. Importantly, CY@D-exos also potently overcomes the senescence of vascular endothelial cells and promotes angiogenesis. In vivo injectable gelatin methacryloyl (GelMA) hydrogels with sustained release of CY@D-exos can accelerate bone injury repair and promote new blood vessel formation in aged animals. Taken together, these results thus demonstrate that cordycepin-loaded dental pulp stem cell-derived exosomes display considerable potential to be developed as a next-generation therapeutic agent for promoting aged bone regeneration and repair.

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Research summary

The paper addresses the rejuvenation of senescent mesenchymal stem cells and endothelial cells, which are critical for bone regeneration, particularly in the context of aging. This focus on cellular senescence and its reversal is relevant to longevity research as it targets mechanisms associated with aging. However, while the findings are solid and contribute to the understanding of bone repair in aged populations, the impact is limited as it primarily addresses a specific application in regenerative medicine rather than a broader understanding of aging mechanisms.

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