Apoptotic Extracellular Vesicles from Supernumerary Tooth-Derived Pulp Stem Cells Transfer COL1A1 to Promote...

Area of Science:

• Cell Biology
• Biomedical Engineering
• Regenerative Medicine

Background:

• Angiogenesis, the formation of new blood vessels, is crucial for development and wound healing.
• Dysfunctional angiogenesis is implicated in various life-threatening diseases.
• Apoptotic extracellular vesicles (ApoEVs) are emerging as safe and efficient proangiogenic agents.

Purpose of the Study:

• To investigate the proangiogenic capacity of ApoEVs derived from supernumerary tooth-derived pulp stem cells (SNTSC-ApoEVs).
• To identify the functional molecules and underlying mechanisms of SNTSC-ApoEVs in promoting angiogenesis.

Main Methods:

• SNTSC-ApoEVs were isolated and characterized.
• In vitro assays (CCK-8, wound healing, transwell, tube formation) assessed effects on human umbilical vein endothelial cells (HUVECs).
• In vivo Matrigel plug assay in mice evaluated micro-vessel formation, complemented by proteomic and RNA sequencing analyses.

Main Results:

• SNTSC-ApoEVs significantly enhanced HUVEC proliferation, migration, and in vitro tube formation.
• In vivo, SNTSC-ApoEVs promoted the formation of CD31-positive luminal structures.
• Proteomic analysis revealed enrichment of extracellular matrix-cell interaction proteins; COL1A1 transfer and PI3K/Akt/VEGF pathway activation were identified as key mechanisms.

Conclusions:

• SNTSC-ApoEVs possess potent proangiogenic properties.
• COL1A1 transfer by SNTSC-ApoEVs activates the PI3K/Akt/VEGF pathway, driving endothelial cell function.
• SNTSC-ApoEVs represent a promising therapeutic strategy for treating angiogenesis-related diseases.