Pro-angiogenic impact of dental stem cells in vitro and in vivo

Within the field of dental tissue engineering, the establishment of adequate tissue vascularization is one of the most important burdens to overcome. As vascular access within the tooth is restricted by the apical foramen, it is of major importance to implement effective vascularization strategies in order to recreate viable components of teeth and periodontal tissues. However, while the current regenerative approaches focus on the use of dental stem cells (DSCs), little is known about these cells and their ability to promote angiogenesis. Therefore, the present study aimed to elucidate the paracrine angiogenic properties of postnatal DSCs, in particular dental pulp stem cells (DPSCs), stem cells from the apical papilla (SCAPs) and dental follicle precursor cells (FSCs). An antibody array, together with RT-PCR and ELISA, pointed out the differential expression of pro-angiogenic as well as anti-angiogenic factors by cultured DSCs and human gingival fibroblasts (HGF-1). Despite the secretion of proliferation-promoting factors, DSCs caused no notable increase in the proliferation of human microvascular endothelial cells (HMEC-1). With regard to other aspects of the angiogenic cascade, DPSCs, SCAPs and HGF-1 significantly promoted endothelial migration in a transwell migration assay. DPSCs also had a pronounced effect on endothelial tubulogenesis, as was shown by an in vitro Matrigel™ assay. In the last part of this study, a chorioallantoic membrane assay demonstrated a sustained pro-angiogenic impact of DPSCs and SCAPs in an in vivo setting. Collectively, these data indicate a predominant pro-angiogenic influence of DPSCs and SCAPS in vitro and in vivo in comparison to FSCs, suggesting that both stem cell populations could potentially promote the vascularization of regenerated dental tissues.