IFATS collection: Adipose stromal cells adopt a proangiogenic phenotype under
the influence of hypoxia.
Authors Thangarajah H, Vial IN, Chang E, El-Ftesi S, Januszyk M, Chang EI, Paterno J,
Neofytou E, Longaker MT, Gurtner GC
Submitted By Geoffrey Gurtner on 3/31/2010
Status Published
Journal Stem Cells
Year 2009
Date Published 2/1/2009
Volume : Pages 27 : 266 - 274
PubMed Reference 18974212
Abstract Evolving evidence suggests a possible role for adipose stromal cells (ASCs) in
adult neovascularization, although the specific cues that stimulate their
angiogenic behavior are poorly understood. We evaluated the effect of hypoxia, a
central mediator of new blood vessel development within ischemic tissue, on
proneovascular ASC functions. Murine ASCs were exposed to normoxia (21% oxygen)
or hypoxia (5%, 1% oxygen) for varying lengths of time. Vascular endothelial
growth factor (VEGF) secretion by ASCs increased as an inverse function of
oxygen tension, with progressively higher VEGF expression at 21%, 5%, and 1%
oxygen, respectively. Greater VEGF levels were also associated with longer
periods in culture. ASCs were able to migrate towards stromal cell-derived
factor (SDF)-1, a chemokine expressed by ischemic tissue, with hypoxia
augmenting ASC expression of the SDF-1 receptor (CXCR4) and potentiating ASC
migration. In vivo, ASCs demonstrated the capacity to proliferate in response to
a hypoxic insult remote from their resident niche, and this was supported by in
vitro studies showing increasing ASC proliferation with greater degrees of
hypoxia. Hypoxia did not significantly alter the expression of endothelial
surface markers by ASCs. However, these cells did assume an endothelial
phenotype as evidenced by their ability to tubularize when seeded with
differentiated endothelial cells on Matrigel. Taken together, these data suggest
that ASCs upregulate their proneovascular activity in response to hypoxia, and
may harbor the capacity to home to ischemic tissue and function cooperatively
with existing vasculature to promote angiogenesis.

Investigators with authorship
Geoffrey GurtnerStanford University


Vegfavascular endothelial growth factor A
Cxcr4chemokine (C-X-C motif) receptor 4