Vascular Cell-Like Potential of Undifferentiated Ligament Fibroblasts to Construct Vascular Cell-Specific Marker-Positive Blood Vessel Structures in a PI3K Activation-Dependent Manner

• Published in: Journal of vascular research Vol. 47; no. 5; pp. 369 - 383
• Main Authors: Okubo, Naoto, Ishisaki, Akira, Iizuka, Tadashi, Tamura, Masato, Kitagawa, Yoshimasa
• Format: Journal Article
• Language: English
• Published: Basel, Switzerland Karger 01.01.2010; S. Karger AG
• Subjects: Animals; Biological and medical sciences; Blood Vessels - growth & development; Cell Lineage; Cell Transdifferentiation; Cells, Cultured; Fibroblasts - cytology; Fibroblasts - physiology; Fundamental and applied biological sciences. Psychology; Male; Mesenchymal Stromal Cells - physiology; Periodontal Ligament - cytology; Phosphatidylinositol 3-Kinases - physiology; Rats; Rats, Wistar; Receptor, TIE-2 - biosynthesis; Research Paper; Signal Transduction; Vascular Endothelial Growth Factor Receptor-2 - biosynthesis; Vertebrates: cardiovascular system; Angiogenesis; Fibroblast growth factor; Endothelial cell; Periodontal ligament; PI3K; Tie-2; FLK-1; Fibroblasts; Three-dimensional vessel reconstruction; Differentiation; Reconstruction; Activation; Marker; Vertebrata; Blood cell; Mammalia; Blood vessel; Circulatory system; Structure; Fibroblast
• ISSN: 1018-1172; 1423-0135
• DOI: 10.1159/000277724

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.