Indispensable Role of HIF-1α Signaling in Post-implantation Survival and Angio-/Vasculogenic Properties of SHED.

objectivesPost-implantation survival and timely vascularization of stem-cell based constructs are critical factors in achieving successful outcomes in tissue regeneration approaches. Hypoxia inducible factor-1α (HIF-1α) is known to mediate adaptive functions to ischemic stress in many different cell types. The current study aimed to explore the role of HIF-1α in post-implantation survival and angio-/vasculogenesis of stem cells from human exfoliated deciduous teeth (SHED).

methodsHIF-1α in SHED was suppressed using siRNA or chemical inhibitor (YC-1) and used in Matrigel plug assay conducted on severe combined immunodeficient mice. The plugs were retrieved on day 3 or 7 post-injection and analyzed for hypoxia status, ki67 expression, DNA fragmentation (TUNEL), cellularity, and vascularization by histology and immunohistochemistry for CD31, HIF-1α, pyruvate dehydrogenase kinase-1 (PDK1), hexokinase 2 (HK2), and glucose transporter 1 (Glut1). Cell viability of HIF-1α silenced SHED under different stress conditions (hypoxia, H

resultsHistological analysis of Matrigel plugs showed significantly reduced cell survival in HIF-1α silenced or chemically inhibited SHED groups, which could be attributed to diminished metabolic adaptations as shown by decreased PDK1, HK2, and Glut1 expression. HIF-1α inhibition in SHED also resulted in significantly low blood vessel formation as observed by a low number of perfused and non-perfused vessels of human or mouse CD31 origin. The viability of HIF-1α silenced SHED was significantly affected under hypoxia, H

conclusionHIF-1α plays an indispensable role in post-implantation survival and angio-/vasculogenic properties of SHED by maintaining ROS homeostasis, inducing metabolic adaptations, and VEGF secretion.