Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation

DNA Cell Biol. 2017 May;36(5):401-412. doi: 10.1089/dna.2016.3546. Epub 2017 Mar 10.

Abstract

The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCsFGF1), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCsFGF1 was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSCFGF1-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p < 0.001). In conclusion, the AD-MSCsFGF1 efficiently secreted functional FGF1, which promoted angiogenic proliferation. Using AD-MSCsFGF1 may provide a useful strategy in cell therapy, which can merge the beneficial effects of stem cells with the positive biological effects of FGF1 in various disorders, especially tissue defects, neurodegenerative, cardiovascular and diabetes endocrine pathologies, which remain to be tested in preclinical and clinical studies.

Keywords: HUVEC tube formation; angiogenesis; cell proliferation; fibroblast growth factor 1; mesenchymal stem cells.

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Cell Proliferation / genetics*
  • Cells, Cultured
  • Fibroblast Growth Factor 1 / genetics*
  • Human Umbilical Vein Endothelial Cells / physiology*
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / physiology*
  • Mice
  • NIH 3T3 Cells
  • Neovascularization, Physiologic / genetics*
  • Rats
  • Rats, Wistar
  • Transfection

Substances

  • Fibroblast Growth Factor 1