Endothelial differentiation of Oral cavity-derived mesenchymal stem/stromal cells

A rapid construction of vasculature ensures the survival and proper functions of tissue-engineered constructs for oral and craniofacial tissue regeneration. Vascularization achieved via a co-culture system containing endothelial cells (ECs) and other supporting cells is more advantageous compared to host angiogenic ingrowth, as it allows faster vessel formation or even prevascularization. Among different sources of ECs, the multidifferentiation capacity of oral cavity-derived mesenchymal stem/stromal cells (MSCs) indicates their potential to give rise to autologous ECs for use in vascular tissue engineering. Considering the growing interest in vascularization in tissue engineering, this review intends to provide a comprehensive overview of the endothelial differentiation of human oral cavity-derived MSCs. Specifically, the author begins by scrutinizing the scientific justification and biological feasibility of employing MSC-derived ECs, followed by an exploration of the criteria and assessment of both in vitro and in vivo endothelial differentiation and a compilation of different strategies for endothelial differentiation induction and their underlying mechanisms. Subsequently, the different aspects pertinent to the practical considerations, including the characteristics and optimization of endothelial differentiation protocols/strategies, culture conditions, and cell origin and subpopulations, are also discussed to guide the selection of the differentiation approach and to understand the factors affecting the differentiation outcome. Finally, the present technical, biological, and clinical constraints and future perspectives are also provided. Gaining a comprehensive knowledge of these topics may provide a cornerstone for the potential derivation of functional and mature ECs from oral cavity-derived MSCs, which will certainly provide clinical value for oral and craniofacial tissue regeneration.