HMSC-Derived VEGF Release Triggers the Chemoattraction of Alveolar Osteoblasts. (12th August 2015)

• Record Type: Journal Article
• Authors: Proksch, Susanne; Bittermann, Gido; Vach, Kirstin; Nitschke, Roland; Tomakidi, Pascal; Hellwig, Elmar
• Is Part Of: Stem cells. Volume 33:Number 10(2015:Oct.)
• Page Start: 3114
• Page End: 3124
• Publication Date: 2015-08-12
• Subjects: Mesenchymal stem cells (MeSH ID D059630) -- Osteoblasts (MeSH ID D010006) -- Chemotaxis (MeSH ID D002633) -- Vascular endothelial growth factor (MeSH ID D042461); Cloning -- Periodicals; Clone cells -- Periodicals; Stem cells -- Periodicals; Cell Differentiation -- Periodicals; Cell Division -- Periodicals; Clone Cells -- Periodicals; Hematopoietic Stem Cells -- Periodicals; Stem Cells -- Periodicals; 571.84
• DOI: 10.1002/stem.2119
• Languages: English
• ISSNs: 1066-5099

Abstract

Abstract: Human mesenchymal stem cells (hMSCs) are promising candidates for regenerative periodontal strategies, due to the broad spectrum of supportive effects on cells and tissues at the site of application. Although positive effects are visible, the understanding of their underlying mechanisms still requires further elucidation. Recently, we have shown that hMSCs are capable to prompt osteogenic differentiation of alveolar osteoblasts, thereby presumably contributing to alveolar bone regeneration. Another issue that is critical in this context is the attraction of hard tissue-forming cells to regeneration sites, but it is an open question whether hMSCs can afford this. In the present manuscript, we show by life cell imaging that in interactive cocultures, hMSCs successfully trigger osteoblast chemotaxis. Gene expression analysis for hMSC-innate chemoattractive biomolecules, orchestrating this process, revealed vascular endothelial growth factor (VEGF), PgE synthase, osteoprotegerin (OPG), monocyte colony-stimulating factor, and transforming growth factor β1, which was confirmed for VEGF and OPG on the protein level. Noteworthy, we showed that only corresponding levels of VEGF but not OPG attracted alveolar osteoblasts similar to hMSC coculture, while VEGF inhibitor abolished both the VEGF and the hMSC-triggered chemoattraction. In summary, we have identified secreted OPG and VEGF proteins as potential chemoattractants, of which further characterization yielded VEGF as a causative for hMSC-directed osteoblast chemotaxis. With respect to the better understanding of potential hMSC-based periodontal regeneration strategies, we propose hMSC-derived VEGF release as a mechanism in the recruitment of hard tissue-forming cells to alveolar bone sites in need of regeneration. Stem Cells 2015;33:3114—3124