VEGFR2-dependent angiogenic capacity of pericyte-like dental pulp stem cells

• Main Authors: K. Janebodin, Y. Zeng, W. Buranaphatthana, N. Ieronimakis, M. Reyes
• Format: Journal
• Published: 2018
• Subjects: Dentistry
• Online Access: https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84877872640&origin=inward; http://cmuir.cmu.ac.th/jspui/handle/6653943832/52476
• Institution: Chiang Mai University

Dental pulp stem cells (DPSCs) have previously demonstrated potential pericyte-like topography and function. However, the mechanisms regulating their pericyte function are still unknown. In this study, murine DPSC angiogenic and pericyte function were investigated. Tie2-GFP mouse DPSCs were negative for GFP, indicating the absence of endothelial cells in DPSC cultures. Endothelial cells co-cultured with DPSCs formed more mature in vitro tube-like structures as compared with those co-cultured with bone marrow stromal cells (BMSCs). Many DPSCs were located adjacent to vascular tubes, assuming a pericyte location. Subcutaneous DPSC transplants in mice with matrigel (MG) (DPSC-MG) induced more vessel formation than BMSC-MG. Soluble Flt (sFlt), an angiogenic inhibitor that binds VEGF-A, significantly decreased the amount of blood vessels in DPSC-MG, but not in BMSC-MG. sFlt inhibited VEGFR2 and downstream ERK signaling in DPSCs. Similar to sFlt inhibition, VEGFR2 knockdown in DPSCs resulted in down-regulation of Vegfa, Vegf receptors, and EphrinB2 and decreased angiogenic induction of DPSCs in vivo. Therefore, the capacity of DPSCs to induce angiogenesis is VEGFR2-dependent. DPSCs enhance angiogenesis by secreting VEGF ligands and associating with vessels resembling pericyte-like cells. This study provides first insights into the mechanism(s) of DPSC angiogenic induction and their function as pericytes, crucial aspects for DPSC use in tissue regeneration. © International & American Associations for Dental Research.