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 in vitro 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.

Impact Statement

This study addresses the limitations of coculturing heterogeneous cell types for bone tissue engineering applications by using gingiva-derived mesenchymal stem cells (GMSCs) as a single, multipotent cell source. GMSCs possess the intrinsic ability to differentiate into osteogenic and endothelial lineages. Specifically, their differentiation into endothelial progenitor-like cells provides a functional alternative source of mature endothelial cells, facilitating angiogenesis and enhancing vascularization, both of which are essential for functional bone regeneration.