Angiogenic Potential and Secretome of XXXX Apical Papilla Mesenchymal Stem Cells in Various Stress Microenvironments.

@entity1 @entity3499 @entity2289 @entity7 @entity2301 @entity26 @entity319 @entity2843 @entity33887 @entity413
UNASSIGNED: Stem cells from the apical papilla ( @entity33887 ) of @entity1 adult teeth are considered an accessible source of cells with angiogenic properties. The aims of this study were to investigate the endothelial transdifferentiation of @entity33887 , the secretion of pro- and antiangiogenic factors from @entity33887 , and the paracrine effects of @entity33887 when exposed to environmental stress to stimulate tissue damage. @entity33887 were exposed to serum deprivation (SD), @entity413 deprivation (GD), and @entity26 deprivation/hypoxia (OD) conditions, individually or in combination. Endothelial transdifferentiation was evaluated by in vitro capillary-like formation assays, real-time polymerase chain reaction, western blot, and flow cytometric analyses of angiogenesis-related markers; secretome by antibody arrays and enzyme-linked immunosorbent assays (ELISA); and paracrine impact on @entity1 umbilical vein endothelial cells (HUVECs) by in vitro transwell migration and capillary-like formation assays. The short-term exposure of @entity33887 to @entity413 / @entity26 deprivation (GOD) in the presence, but mainly in deprivation, of serum (SGOD) elicited a proangiogenesis effect indicated by expression of angiogenesis-related genes involved in @entity7 ( @entity7 )/ @entity319 and angiopoietins/Tie pathways. This effect was unachievable under SD in normoxia, suggesting that the critical microenvironmental condition inducing rapid endothelial shift of @entity33887 is the combination of SGOD. Interestingly, @entity33887 showed high adaptability to these adverse conditions, retaining cell viability and acquiring a capillary-forming phenotype. @entity33887 secreted higher numbers and amounts of pro- (angiogenin, @entity2301 , @entity7 ) and lower amounts of antiangiogenic factors ( @entity2289 , @entity2843 , @entity3499 ) under SGOD compared with SOD or SD alone. Finally, secretome obtained under SGOD was most effective in inducing migration and capillary-like formation by HUVECs. These data provide new evidence on the microenvironmental factors favoring endothelial transdifferentiation of @entity33887 , uncovering the molecular mechanisms regulating their fate. They also validate the angiogenic properties of their secretome giving insights into preconditioning strategies enhancing their therapeutic potential.
