Ang1/Tie2/VE-Cadherin Signaling Regulates DPSCs in Vascular Maturation

Area of Science:

• Regenerative Medicine
• Vascular Biology
• Stem Cell Therapy

Background:

• Dental pulp stem cells (DPSCs) exhibit pericyte-like functions and support endothelial cell (EC) networks.
• The precise mechanisms by which DPSC-derived pericytes stabilize vasculature remain incompletely understood.

Purpose of the Study:

• To investigate the vascular stabilizing functions of E-DPSCs and T-DPSCs in vitro and in vivo.
• To elucidate the molecular mechanisms underlying the enhanced vascular stabilization by modified DPSCs.

Main Methods:

• In vitro: 3D coculture spheroid sprouting assay comparing E-DPSCs and T-DPSCs.
• In vivo: Angiogenesis assessment in severe combined immunodeficiency (SCID) mouse models.
• Molecular analysis of signaling pathways including Tie2, VE-cadherin, and VEGFR2.

Main Results:

• Both E-DPSCs and T-DPSCs demonstrated smooth muscle cell-like properties and suppressed EC sprouting.
• Modified DPSCs stabilized blood vessels by activating Angiopoietin 1 (Ang1)/Tie2 signaling and upregulating VE-cadherin.
• In vivo studies showed increased vessel perfusion and total vessel count in groups treated with E-DPSCs or T-DPSCs.

Conclusions:

• E-DPSCs and T-DPSCs effectively stabilize newly formed blood vessels and enhance perfusion.
• The Ang1/Tie2/VE-cadherin and VEGF/VEGFR2 signaling pathways are critical for DPSC-mediated vascular stabilization.