Vascular cell-like potential of undifferentiated ligament fibroblasts to construct vascular cell-specific marker-positive blood vessel structures in a PI3K activation-dependent manner

J Vasc Res. 2010;47(5):369-83. doi: 10.1159/000277724. Epub 2010 Jan 27.


Objective: To evaluate whether fibroblasts derived from periodontal ligament retain the ability to differentiate into putative vascular cells and construct vascular cell-specific marker-positive blood vessel structures. We also evaluated the morphological features of the structure and investigated the intracellular molecular mechanism underlying the angiogenic activity of these cells.

Methods: Single cell-derived cultures (SCDCs) were established from primary rat ligament fibroblast cultures, and their expression of ligament cell-, mesenchymal stem cell- and vascular cell-specific markers was evaluated by RT-PCR and immunocytochemistry. The ability of the cells to construct a blood vessel structure was evaluated in a three-dimensional type I collagen scaffold. The morphological and immunohistological characteristics of the structure were then evaluated.

Results: Each SCDC expressed endothelial cell (EC)-specific and smooth muscle cell-specific markers, in addition to mesenchymal stem cell- and ligament cell-specific markers. SCDC2 cells, which abundantly expressed the EC markers Flk-1 and Tie-2, vigorously constructed a blood vessel structure in a phosphoinositide 3-kinase activation-dependent manner.

Conclusion: Periodontal ligament fibroblasts have the potential to construct an EC marker-positive blood vessel-like structure. Consequently, the fibroblastic lineage in ligament tissue could be a candidate precursor for construction of a vascular system around damaged ligament tissue to facilitate its regeneration.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / growth & development*
  • Cell Lineage
  • Cell Transdifferentiation*
  • Cells, Cultured
  • Fibroblasts / cytology
  • Fibroblasts / physiology*
  • Male
  • Mesenchymal Stem Cells / physiology
  • Periodontal Ligament / cytology*
  • Phosphatidylinositol 3-Kinases / physiology
  • Rats
  • Rats, Wistar
  • Receptor, TIE-2 / biosynthesis
  • Signal Transduction
  • Vascular Endothelial Growth Factor Receptor-2 / biosynthesis


  • Phosphatidylinositol 3-Kinases
  • Receptor, TIE-2
  • Vascular Endothelial Growth Factor Receptor-2