Document Detail

Hypoxic conditioning enhances the angiogenic paracrine activity of human adipose-derived stem cells.
MedLine Citation:
PMID:  23282141     Owner:  NLM     Status:  Publisher    
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 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 VEGF-A and angiogenin (ANG). The angiogenicity of ASC conditioned media (ASCCM) was assessed by implanting ASCCM-treated polyvinyl alcohol sponges subcutaneously for 2 weeks in mice. Morphometric analysis of anti-CD31-immunolabelled sponge sections demonstrated increased angiogenesis with hypoxic ASCCM treatment compared to normoxic control ASCCM treatment (percentage vascular volume; 6.0 ± 0.5% in hypoxic ASCCM vs. 4.1 ± 0.7% in normoxic ASCCM, p < 0.05). Reduction of VEGF-A and ANG levels in ASCCM with respective neutralising antibodies before sponge implantation showed 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). Furthermore, both normoxic and hypoxic ASCCM were able to sustain in vivo lymphangiogenesis in sponges. Collectively, the model demonstrated that the increased paracrine production of VEGF-A and ANG in hypoxic-conditioned ASCs in vitro translated to an in vivo effect with favourable biological significance. These results further illustrate the potential for utilisation of in vitro optimised ASCCM for in vivo angiogenesis-related applications as an effective cell-free technology.
Sarah Tzu-Feng Hsiao; Zerina Lokmic; Hitesh Peshavariya; Keren M Abberton; Gregory J Dusting; Shiang Yong Lim; Rodney J Dilley
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-1-2
Journal Detail:
Title:  Stem cells and development     Volume:  -     ISSN:  1557-8534     ISO Abbreviation:  Stem Cells Dev.     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-1-3     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101197107     Medline TA:  Stem Cells Dev     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
O'Brien Institute, Fitzroy, Victoria, Australia, , University of Melbourne, Department of Surgery, Fitzroy, Victoria, Australia;
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Multi-species data integration and gene ranking enrich significant results in an alcoholism genome-w...
Next Document:  Discovery of a new class of inhibitors for the protein arginine deiminase type 4 (PAD4) by structure...