Generation of induced endothelial and neural progenitor cells from dental stem cells for angiogenesis and neurogenesis

Abstract

Integration of angiogenesis and neurogenesis into pulp tissue constructs is essential for pulp/dentin complex regeneration. One promising strategy to enhance angiogenesis is to incorporate pre-made microvascular networks into the engineered constructs. This allows timely connection with the host circulation after implantation to ensure blood supply within the tissue constructs. Most studies on vascular bioengineering have used primary vascular cells and vascular cells derived from embryonic, induced pluripotent, and endothelial progenitor cells. Nevertheless, there are numerous challenges in using these cells clinically. We recently transdifferentiated dental stem cells into endothelial cells (iECs) using a cocktail of small molecules. The iECs displayed similar endothelial properties to that of corresponding primary vascular cells. The iECs could be used to prevascularize the pulp construct for dental pulp regeneration, and thus only a single cell source for the prevascularization is needed. Our group has also successfully reprogrammed dental stem cells into iNPCs. These iNPCs display strong expression of neural markers and possess enhanced physiological functionalities of neuronal lineages. In addition, we investigated to transdifferentiate one cell source to achieve vascularization, innervation and dentin formation. The generated iECs and iNPCs will be promising resources for engineering the vasculature and neural tissue during pulp regeneration.