The effect of bisphosphonates on the endothelial differentiation of mesenchymal stem cells

• Published in: Scientific reports Vol. 6; no. 1; p. 20580
• Main Authors: Sharma, Dileep, Hamlet, Stephen Mark, Petcu, Eugen Bogdan, Ivanovski, Saso
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-02-2016; Nature Publishing Group
• Subjects: 13/100; 13/106; 13/21; 14/1; 14/19; 14/34; 38/39; 38/77; 631/80/304; 692/699/3020; Antigens, Differentiation - biosynthesis; Bisphosphonates; Cell adhesion & migration; Cell differentiation; Cell Differentiation - drug effects; Cells, Cultured; Cytotoxicity; Diphosphonates - pharmacology; Dose-Response Relationship, Drug; Endothelial Cells - cytology; Endothelial Cells - metabolism; Female; Gene expression; Gene Expression Regulation - drug effects; Humanities and Social Sciences; Humans; Immunology; Mesenchymal stem cells; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - metabolism; Mesenchyme; multidisciplinary; Nitrogen; Progenitor cells; Science; Science (multidisciplinary); Stem cells
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep20580

The contribution of the local stem cell niche to providing an adequate vascular framework during healing cannot be overemphasized. Bisphosphonates (BPs) are known to have a direct effect on the local vasculature, but their effect on progenitor cell differentiation is unknown. This
in vitro
study evaluated the effect(s) of various BPs on the differentiation of human placental mesenchymal stem cells (pMSCs) along the endothelial lineage and their subsequent functional and morphogenic capabilities. pMSC multipotency was confirmed by successful differentiation into cells of both the osteogenic and endothelial lineages, as demonstrated by positive Alizarin Red S staining and Ac-LDL uptake. pMSC differentiation in the presence of non-cytotoxic BP concentrations showed that nitrogen containing BPs had a significant inhibitory effect on cell migration and endothelial marker gene expression, as well as compromised endothelial differentiation as demonstrated using von Willebrand factor immunofluorescence staining and tube formation assay. This
in vitro
study demonstrated that at non-cytotoxic levels, nitrogen-containing BPs inhibit differentiation of pMSCs into cells of an endothelial lineage and affect the downstream functional capability of these cells supporting a multi-modal effect of BPs on angiogenesis as pathogenic mechanism contributing to bone healing disorders such as bisphosphonate related osteonecrosis of the jaws (BRONJ).