VEGF-A-Mediated Differentiation of Gingival Stem Cells to Endothelial Progenitor-Like Cells.

Abstract

The clinical success of bone regeneration relies on developing a functional, vascularized bone. Insufficient vascularization of tissue constructs remains a challenge in stem cell-based approaches, leading to poor graft integration and necrosis of newly formed bone. To overcome current challenges, using pre-committed stem cells for endothelial lineages is a novel approach to developing a vascularized tissue construct. Human gingiva-derived mesenchymal stem cells (GMSCs) are a unique cell population that is readily accessible, has a high proliferation rate, and exhibits multipotent differentiation. This study aimed to investigate the <i>in vitro</i> differentiation potential of GMSCs into the endothelial lineage. GMSCs were induced with 0, 10, 50, or 100 ng/mL recombinant vascular endothelial growth factor (VEGF) for 1 week. The relative mRNA expressions of vascular cell adhesion molecule 1, protocadherin 12, VEGF receptor 1 (fms-like tyrosine kinase 1), VEGF receptor 2 (kinase insert domain receptor), and platelet endothelial cell adhesion molecule-1 were measured by quantitative reverse transcriptase polymerase chain reaction. The expression of all endothelial marker mRNAs was significantly upregulated in a dose-dependent manner in GMSCs induced by VEGF, and maximum expression was observed at 50 ng/mL VEGF induction. A Matrigel assay demonstrated the tube-forming ability of pre-differentiated GMSCs. Our findings demonstrated that GMSCs have the potential to differentiate into endothelial progenitor-like cells. Thus, our study identifies potential options for using GMSCs as an autologous or allogeneic stem cell source for craniofacial bone regeneration.