ASC Spheroid Geometry and Culture Oxygenation Differentially Impact Induction of Preangiogenic Behaviors in Endothelial Cells
| Autor: | Ehsan Jabbarzadeh, Matthew L. Skiles, Brandon William Hanna, Lindsay Rucker, Allison Tipton, James O. Blanchette, Aidan Brougham-Cook |
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| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Vascular Endothelial Growth Factor A
Umbilical Veins Angiogenesis medicine.medical_treatment Biomedical Engineering Cell Culture Techniques lcsh:Medicine Neovascularization Physiologic Biology Article Spheroids Cellular medicine Humans Transplantation Growth factor lcsh:R Mesenchymal stem cell Spheroid Endothelial Cells Mesenchymal Stem Cells Cell Biology Anatomy Cell Hypoxia Oxygen tension Cell biology Vascular endothelial growth factor A Adipose Tissue Cell culture Culture Media Conditioned embryonic structures Stem cell |
| Zdroj: | Cell Transplantation, Vol 24 (2015) |
| Popis: | Cell-based angiogenic therapies offer potential for the repair of ischemic injuries, while avoiding several of the limitations associated with material-based growth factor delivery strategies. Evidence supports that applying MSCs as spheroids rather than dispersed cells can improve retention and enhance therapeutic effect through increased secretion of angiogenic factors due to hypoxia. However, while spheroid culture appears to modulate MSC behavior, there has been little investigation of how major culture parameters that affect cellular oxygen tension, such as external oxygenation and culture size, impact the angiogenic potential of spheroids. We cultured equal numbers of adipose-derived stem cells (ASCs) as spheroids containing 10,000 (10k) or 60,000 (60k) cells each, in 20% and 2% oxygen. VEGF secretion varied among the sample groups, with 10k, 2% O2 spheroids exhibiting the highest production. Spheroid-conditioned media was applied to HUVEC monolayers, and proliferation was assessed. Spheroids of either size in 2% oxygen induced comparable proliferation compared to a 2 ng/ml VEGF control sample, while spheroids in 20% oxygen induced less proliferation. Spheroids were also applied in coculture with HUVEC monolayers, and induction of migration through a Transwell membrane was evaluated. Sixty thousand, 2% O2 spheroids induced similar levels of migration as VEGF controls, while 10k, 2% O2 spheroids induced significantly more. Ten thousand, 20% spheroids performed no better than VEGF-free controls. We conclude that the therapeutic ability of ASC spheroids to stimulate angiogenesis in endothelial cells is affected by both culture size and oxygenation parameters, suggesting that, while ASC spheroids offer potential in the treatment of injured and ischemic tissues, careful consideration of culture size in respect to in vivo local oxygen tension will be necessary for optimal results. |
| Databáze: | OpenAIRE |
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