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Angiogenic properties of aged adipose derived mesenchymal stem cells after hypoxic conditioning

: Efimenko, Anastasia; Starostina, Ekaterina; Kalinina, Natalia; Stolzing, Alexandra

Postprint (684 KByte; PDF; )

Journal of translational medicine 9 (2011), Nr.10, 13 S.
ISSN: 1479-5876
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer IZI ()

Background: Mesenchymal stem cells derived from adipose tissue (ADSC) are multipotent stem cells, originated
from the vascular-stromal compartment of fat tissue. ADSC are used as an alternative cell source for many different
cell therapies, however in ischemic cardiovascular diseases the therapeutic benefit was modest. One of the reasons
could be the use of autologous aged ADSC, which recently were found to have impaired functions. We therefore
analysed the effects of age on age markers and angiogenic properties of ADSC. Hypoxic conditioning was
investigated as a form of angiogenic stimulation.
Methods: ADSC were harvested from young (1-3 month), adult (12 month) and aged (18-24 month) mice and
cultured under normoxic (20%) and hypoxic (1%) conditions for 48 h. Differences in proliferation, apoptosis and
telomere length were assessed in addition to angiogenic properties of ADSC.
Results: Proliferation potential and telomere length were decreased in aged ADSC compared to young ADSC.
Frequency of apoptotic cells was higher in aged ADSC. Gene expression of pro-angiogenic factors including
vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and hepatic growth factor (HGF) were
down-regulated with age, which could be restored by hypoxia. Transforming growth factor (TGF-b) increased in
the old ADSC but was reduced by hypoxia.
Expression of anti-angiogenic factors including thrombospondin-1 (TBS1) and plasminogen activator inhibitor-1
(PAI-1) did increase in old ADSC, but could be reduced by hypoxic stimulation. Endostatin (ENDS) was the highest
in aged ADSC and was also down-regulated by hypoxia. We noted higher gene expression of proteases system
factors like urokinase-type plasminogen activator receptor (uPAR), matrix metalloproteinases (MMP2 and MMP9)
and PAI-1 in aged ADSC compared to young ADSC, but they decreased in old ADSC. Tube formation on matrigel
was higher in the presence of conditioned medium from young ADSC in comparison to aged ADSC.
Conclusions: ADSC isolated from older animals show changes, including impaired proliferation and angiogenic
stimulation. Angiogenic gene expression can be partially be improved by hypoxic preconditioning, however the
effect is age-dependent. This supports the hypothesis that autologous ADSC from aged subjects might have an
impaired therapeutic potential.