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

Oral Dis. 2020 Apr 5. doi: 10.1111/odi.13341. Online ahead of print.


Objectives: We aimed to investigate whether the mesenchymal stem cell-endothelial cell crosstalk enhances angiogenic factor expression via nuclear factor-kappa B (NF-κB)-dependent mechanisms.

Materials and methods: Human dermal microvascular endothelial cells (HDMECs) and stem cells from human exfoliated deciduous teeth (SHEDs) were cocultured for 96 hr, in the presence of NF-κB decoy oligodeoxynucleotides (ODNs) or scramble (control). Vascular endothelial cell growth factor (VEGF) and phospho-NF-κB p65 were measured with enzyme-linked immunosorbent assay. Angiogenesis-related gene expression was analyzed with microarray analysis followed by real-time polymerase chain reaction. Tube formation assay was conducted in the presence of NF-κB decoy.

Results: The VEGF and phospho-NF-κB p65 levels were significantly higher in the coculture with NF-κB decoy scramble than in single culture and coculture with NF-κB decoy ODN. Microarray analysis of SHEDs and HDMECs with NF-κB decoy scramble showed higher expression of proangiogenic genes, Bcl-2, NF-κB1, VEGFA, CXCL8, and CXCR1, and lower expression of proapoptotic genes, Bax and Caspase 9, compared to cells with NF-κB decoy ODN. Real-time PCR results for Bcl-2 and CXCL8 showed a similar trend. Tube formation assay showed more tube development in the presence of NF-κB decoy scramble.

Conclusion: The SHED-HDMEC crosstalk enhanced proangiogenic factor expression via NF-κB-dependent pathways.

Keywords: B-cell lymphoma 2; chemokine (C-X-C motif) ligand 8; endothelial cell; nuclear factor-κB; stem cells from human exfoliated deciduous teeth; vascular endothelial growth factor.