Document Detail

Hypoxic conditioning enhances the angiogenic paracrine activity of human adipose-derived stem cells.
MedLine Citation:
PMID:  23282141     Owner:  NLM     Status:  MEDLINE    
Human adipose-derived stem cells (ASCs) secrete cytokines and growth factors that can be harnessed in a paracrine fashion for promotion of angiogenesis, cell survival, and activation of endogenous stem cells. We recently showed that hypoxia is a powerful stimulus for an angiogenic activity from ASCs in vitro and here we investigate the biological significance of this paracrine activity in an in vivo angiogenesis model. A single in vitro exposure of ASCs to severe hypoxia (<0.1% O2) significantly increased both the transcriptional and translational level of the vascular endothelial growth factor-A (VEGF-A) and angiogenin (ANG). The angiogenicity of the ASC-conditioned medium (ASC(CM)) was assessed by implanting ASC(CM)-treated polyvinyl alcohol sponges subcutaneously for 2 weeks in mice. The morphometric analysis of anti-CD31-immunolabeled sponge sections demonstrated an increased angiogenesis with hypoxic ASC(CM) treatment compared to normoxic control ASC(CM) treatment (percentage vascular volume; 6.0%±0.5% in the hypoxic ASC(CM) vs. 4.1%±0.7% in the normoxic ASC(CM), P<0.05). Reduction of VEGF-A and ANG levels in the ASC(CM) with respective neutralizing antibodies before sponge implantation showed a significantly diminished angiogenic response (3.5%±0.5% in anti-VEGF-A treated, 3.2%±0.7% in anti-ANG treated, and 3.5%±0.6% in anti-VEGF-A/ANG treated). Further, both the normoxic and hypoxic ASC(CM) were able to sustain in vivo lymphangiogenesis in sponges. Collectively, the model demonstrated that the increased paracrine production of the VEGF-A and ANG in hypoxic-conditioned ASCs in vitro translated to an in vivo effect with a favorable biological significance. These results further illustrate the potential for utilization of an in vitro optimized ASC(CM) for in vivo angiogenesis-related applications as an effective cell-free technology.
Sarah T Hsiao; Zerina Lokmic; Hitesh Peshavariya; Keren M Abberton; Gregory J Dusting; Shiang Y Lim; Rodney J Dilley
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2013-03-15
Journal Detail:
Title:  Stem cells and development     Volume:  22     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 May 
Date Detail:
Created Date:  2013-05-08     Completed Date:  2014-02-20     Revised Date:  2014-05-16    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1614-23     Citation Subset:  IM    
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MeSH Terms
Adipose Tissue / cytology*
Cell Hypoxia / drug effects
Culture Media, Conditioned / pharmacology
Mice, Inbred C57BL
Neovascularization, Physiologic* / drug effects
Oxygen / pharmacology
Paracrine Communication* / drug effects
Ribonuclease, Pancreatic / genetics,  metabolism
Stem Cells / cytology,  drug effects,  metabolism*
Vascular Endothelial Growth Factor A / genetics,  metabolism
Vascular Endothelial Growth Factor C / genetics,  metabolism
Reg. No./Substance:
0/Culture Media, Conditioned; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factor C; EC 3.1.27.-/angiogenin; EC, Pancreatic; S88TT14065/Oxygen

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