Abstract
ObjectivesRecently, a new strategy has been developed to directly reprogram one cell type towards another targeted cell type using small molecule compounds. Human fibroblasts have been chemically reprogrammed into neuronal cells, Schwann cells and cardiomyocyte-like cells by different small molecule combinations. This study aimed to explore whether stem cells from apical papilla (SCAP) could be reprogrammed into endothelial cells (ECs) using the same strategy.Materials and methodsThe expression level of endothelial-specific genes and proteins after chemical induction of SCAP was assessed by RT-PCR, western blotting, flow cytometry and immunofluorescence. The in vitro functions of SCAP-derived chemical-induced endothelial cells (SCAP-ECs) were evaluated by tube-like structure formation assay, acetylated low-density lipoprotein (ac-LDL) uptake and NO secretion detection. The proliferation and the migration ability of SCAP-ECs were evaluated by CCK-8 and Transwell assay. LPS stimulation was used to mimic the inflammatory environment in demonstrating the ability of SCAP-ECs to express adhesion molecules. The in vivo Matrigel plug angiogenesis assay was performed to assess the function of SCAP-ECs in generating vascular structures using the immune-deficient mouse model.ResultsSCAP-ECs expressed upregulated endothelial-specific genes and proteins; displayed endothelial transcriptional networks; exhibited the ability to form functional tubular-like structures, uptake ac-LDL and secrete NO in vitro; and contributed to generate blood vessels in vivo. The SCAP-ECs could also express adhesion molecules in the pro-inflammatory environment and have a similar migration and proliferation ability as HUVECs.ConclusionsOur study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of SCAP, which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases.
Highlights
Postnatal angiogenesis plays an essential role in the recovery of ischemic tissues and survival of engineered tissue constructs after implantation [1, 2]
Our study demonstrates that the set of small molecules and growth factors could significantly promote endothelial transdifferentiation of stem cells from apical papilla (SCAP), which provides a promising candidate cell source for vascular engineering and treatment of ischemic diseases
Reprogramming SCAP into endothelial-like cells by small molecule cocktail We have recently demonstrated that TGF-β signalling inhibitor SB431452 could significantly enhance the capacity of vascular endothelial growth factor (VEGF) to induce Stem cells from human exfoliated deciduous teeth (SHED) differentiation into endothelial cells (ECs) [24]
Summary
Postnatal angiogenesis plays an essential role in the recovery of ischemic tissues and survival of engineered tissue constructs after implantation [1, 2] During this process, locally elevated angiogenic factors, such as vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), activate endothelial cells’ proliferation, migration and self-assembling to form primitive vascular networks, which is followed by stepwise mural cell recruitment and stabilization of the nascent vessels [3]. For vascular tissue engineering and its translational application, the first step is to obtain adequate number of ECs. Autologous endothelial cells like human umbilical vein endothelial cells (HUVECs) and human microvascular endothelial cells (HMECs) are the most suitable cell sources for vascularization. Dental-derived stem cells, which express several pluripotency markers not usually expressed by other adult stem cells, such as SOX2, NANOG and OCT4, could be a potential substitute cell source for endothelial differentiation [14]
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