Crosstalk between dental pulp stem cells and endothelial cells augments angiogenic factor expression

Area of Science:

• Regenerative Medicine
• Cell Biology
• Molecular Biology

Background:

• Mesenchymal stem cells (MSCs) and endothelial cells (ECs) interact to regulate tissue repair and angiogenesis.
• The role of nuclear factor-kappa B (NF-κB) signaling in MSC-EC crosstalk and its impact on angiogenic factor expression requires further elucidation.

Purpose of the Study:

• To investigate the role of NF-κB-dependent mechanisms in mediating the proangiogenic effects of stem cell-endothelial cell crosstalk.
• To determine if stem cells from human exfoliated deciduous teeth (SHEDs) and human dermal microvascular endothelial cells (HDMECs) crosstalk enhances angiogenic factor expression via NF-κB.

Main Methods:

• SHEDs and HDMECs were cocultured with or without NF-κB decoy oligodeoxynucleotides (ODNs).
• Vascular endothelial cell growth factor (VEGF) and phospho-NF-κB p65 levels were quantified using ELISA.
• Gene expression profiling of angiogenesis-related genes was performed using microarray and real-time PCR.
• In vitro tube formation assays were conducted to assess angiogenic potential.

Main Results:

• Coculture of SHEDs and HDMECs significantly increased VEGF and phospho-NF-κB p65 levels compared to single cultures.
• NF-κB inhibition with decoy ODNs reduced the expression of proangiogenic genes (e.g., VEGFA, CXCL8) and increased proapoptotic genes (e.g., Bax, Caspase 9).
• Microarray and real-time PCR confirmed enhanced expression of proangiogenic factors and suppressed proapoptotic factors in cocultures without NF-κB inhibition.
• Tube formation assays demonstrated increased vascular network formation in cocultures with intact NF-κB signaling.

Conclusions:

• SHED-HDMEC crosstalk promotes angiogenesis through NF-κB-dependent pathways.
• The study highlights the critical role of NF-κB signaling in mediating the proangiogenic potential of stem cell-endothelial cell interactions.