Endocrine Abstracts

Wound healing and tumour stroma formation are associated with angiogenesis and require interactions of various different cell types. We and others have shown that mesenchymal stem cells (MSCs) differentiate into fibroblast-/pericyte-like cells and secrete proangiogenic factors. Thyroid hormones act as proangiogenic modulators mediated by non-genomic mechanisms via cell surface receptor integrin αvβ3. The aim of this study is to evaluate the stimulatory activity of T3 and T4 on endothelial cell tube formation in concert with the assessment of angiogenic effects of MSCs.

Primary human umbilical vein endothelial cells (HUVECs) were seeded on Matrigel and tube formation was analysed microscopically. Treatment with T3 stimulated tube formation as evidenced by a larger number of junctions and meshes and an increased total tube length compared to untreated cells. Additional treatment with tetrac, a specific inhibitor of integrin αvβ3-mediated action of T3/T4, reduced tube formation to basal level. Similar, albeit weaker, effects were observed for T4. Further, primary human bone marrow-derived MSC-conditioned medium stimulated tube formation. After additional treatment with T3, an even more pronounced angiogenic effect was observed compared to untreated control cells and tetrac-treated cells. In a further set of experiments, co-cultures of HUVECs and MSCs were analysed in this assay. MSCs were found to be integrated into developing tubular networks adjacent to HUVECs - a system that we are now employing to elucidate effects of thyroid hormones on HUVEC-MSC interactions.

Our data suggest that thyroid hormones T3 and T4 stimulate angiogenesis in HUVECs in an integrin αvβ3-dependent manner, an effect that can be enhanced by additional treatment with MSC-conditioned medium. These studies improve our understanding of the critical role of thyroid hormone in the regulation of angiogenesis both in the context of wound healing and tumour stroma formation.