scholarly journals Level of Vascular Endothelial Growth Factor Predicts Both Relapse and Nonrelapse Mortality after Allogeneic Hematopoietic Stem Cell Transplantation

2013 ◽  
Vol 19 (12) ◽  
pp. 1677-1682 ◽  
Author(s):  
Ivan S. Moiseev ◽  
Sergey V. Lapin ◽  
Elena A. Surkova ◽  
Margarita Y. Lerner ◽  
Vladimir N. Vavilov ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Stem Cell ◽  
Growth Factor ◽  
Hematopoietic Stem Cell Transplantation ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Hematopoietic Stem Cell ◽  
Vascular Endothelial ◽  
Hematopoietic Stem ◽  
Endothelial Growth Factor

scholarly journals Hypoxic induction of vascular endothelial growth factor regulates murine hematopoietic stem cell function in the low-oxygenic niche

Blood ◽  
2011 ◽  
Vol 118 (6) ◽  
pp. 1534-1543 ◽  
Author(s):  
Matilda Rehn ◽  
André Olsson ◽  
Kristian Reckzeh ◽  
Eva Diffner ◽  
Peter Carmeliet ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Stem Cell ◽  
Growth Factor ◽  
Hematopoietic Stem Cell ◽  
Molecular Mechanisms ◽  
Cell Function ◽  
Vascular Endothelial ◽  
Low Oxygen ◽  
Hematopoietic Stem ◽  
Endothelial Growth Factor

Abstract Hypoxia is emerging as an important characteristic of the hematopoietic stem cell (HSC) niche, but the molecular mechanisms contributing to quiescence, self-renewal, and survival remain elusive. Vascular endothelial growth factor A (VEGFA) is a key regulator of angiogenesis and hematopoiesis. Its expression is commonly regulated by hypoxia-inducible factors (HIF) that are functionally induced in low-oxygen conditions and that activate transcription by binding to hypoxia-response elements (HRE). Vegfa is indispensable for HSC survival, mediated by a cell-intrinsic, autocrine mechanism. We hypothesized that a hypoxic HSC microenvironment is required for maintenance or up-regulation of Vegfa expression in HSCs and therefore crucial for HSC survival. We have tested this hypothesis in the mouse model Vegfaδ/δ, where the HRE in the Vegfa promoter is mutated, preventing HIF binding. Vegfa expression was reduced in highly purified HSCs from Vegfaδ/δ mice, showing that HSCs reside in hypoxic areas. Loss of hypoxia-regulated Vegfa expression increases the numbers of phenotypically defined hematopoietic stem and progenitor cells. However, HSC function was clearly impaired when assessed in competitive transplantation assays. Our data provide further evidence that HSCs reside in a hypoxic microenvironment and demonstrate a novel way in which the hypoxic niche affects HSC fate, via the hypoxia-VEGFA axis.

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