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Open Access Research

Identical effects of VEGF and serum-deprivation on phenotype and function of adipose-derived stromal cells from healthy donors and patients with ischemic heart disease

Bjarke Follin1, Josefine Tratwal1, Mandana Haack-Sørensen1, Jens Jørgen Elberg2, Jens Kastrup1 and Annette Ekblond1*

Author Affiliations

1 Cardiology Stem Cell Center, The Heart Center, Rigshospitalet, University Hospital Copenhagen, Copenhagen, Denmark

2 Department of Plastic Surgery, Rigshospitalet, University Hospital Copenhagen, Copenhagen, Denmark

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Journal of Translational Medicine 2013, 11:219  doi:10.1186/1479-5876-11-219

Published: 18 September 2013

Abstract

Background

Adipose-derived stromal cells (ASCs) stimulated with vascular endothelial growth factor (VEGF) and serum-deprived, are applied in the first in-man double-blind placebo-controlled MyStromalCell Trial, as a novel therapeutic option for treatment of ischemic heart disease (IHD). This in vitro study explored the effect of VEGF and serum deprivation on endothelial differentiation capacity of ASCs from healthy donors and IHD patients.

Methods

ASCs stimulated with rhVEGFA165 in serum-deprived medium for one to three weeks were compared with ASCs in serum-deprived (2% fetal bovine serum) or complete medium (10% fetal bovine serum). Expression of VEGF receptors, endothelial and stem cell markers was measured using qPCR, flow cytometry and immunocytochemistry. In vitro tube formation and proliferation was also measured.

Results

ASCs from VEGF-stimulated and serum-deprived medium significantly increased transcription of transcription factor FOXF1, endothelial marker vWF and receptor VEGFR1 compared with ASCs from complete medium. ASCs maintained stem cell characteristics in all conditions. Tube formation of ASCs occurred in VEGF-stimulated and serum-deprived medium. The only difference between healthy and patient ASCs was a variation in proliferation rate.

Conclusions

ASCs from IHD patients and healthy donors proved equally inclined to differentiate in endothelial direction by serum-deprivation, however with no visible additive effect of VEGF stimulation. The treatment did not result in complete endothelial differentiation, but priming towards endothelial lineage.

Keywords:
Angiogenesis; Adipose-derived stromal cells; VEGF