Adipose tissue-derived stromal cells acquire endothelial-like features upon reprogramming with SOX18

R.D. Fontijn, J. Favre, B.A. Naaijkens, E. Meinster, N.J. Paauw, S.L. Ragghoe, T.D. Nauta, M.A. van den Broek, E.M. Weijers, H.W.M. Niessen, P. Koolwijk, A.J.G. Horrevoets

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16 Citations (Scopus)

Abstract

Adipose tissue-derived stromal cells (ASC) form a rich source of autologous cells for use in regenerative medicine. In vitro induction of an endothelial phenotype may improve performance of ASCs in cardiovascular repair. Here, we report on an in vitro strategy using direct reprogramming of ASCs by means of ectopic expression of the endothelial-specific transcription factor SRY (sex determining region Y)-box18 (SOX18). SOX18 induces ASCs to express a set of genes involved in vascular patterning: MMP7, KDR, EFNB2, SEMA3G and CXCR4. Accordingly, SOX18 transduced ASCs reorganize under conditions of shear stress, display VEGF-induced chemotaxis and form tubular structures in 3D matrices in an MMP7-dependent manner. These in vitro findings provide insight into molecular and cellular processes downstream of SOX18 and show that reprogramming using SOX18 is sufficient to induce several endothelial-like features in ASCs.

Original languageEnglish
Pages (from-to)367-378
Number of pages12
JournalStem Cell Research
Volume13
Issue number3 Pt A
DOIs
Publication statusPublished - Nov 2014

Keywords

  • Adipose Tissue
  • Cell Differentiation
  • Cell Movement
  • Cells, Cultured
  • Cellular Reprogramming
  • Chemotaxis
  • Endothelial Cells
  • Genetic Vectors
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Journal Article
  • Matrix Metalloproteinase 7
  • Microtubules
  • Research Support, Non-U.S. Gov't
  • SOXF Transcription Factors
  • Shear Strength
  • Stromal Cells
  • Vascular Endothelial Growth Factor A

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