Extracellular vesicles from endothelial progenitor cells promote thyroid follicle formation

J Extracell Vesicles. 2018 Jun 28;7(1):1487250. doi: 10.1080/20013078.2018.1487250. eCollection 2018.

Abstract

Organogenesis is a complex and dynamic process requiring reciprocal communication between different cell types. In the thyroid, thyrocyte progenitors secrete the angiocrine factor, VEGFA, to recruit endothelial cells. In return, endothelial cells promote thyrocyte organisation into spherical follicular structures, which are responsible for thyroid hormone synthesis and storage. Medium conditioned by endothelial progenitor cells (EPCs) can promote follicle formation and lumen expansion (i.e. folliculogenesis) in an ex vivo culture system of thyroid lobes. Here, we postulated that endothelial cells instruct thyrocyte progenitors by producing extracellular vesicles (EVs). We found that medium conditioned by EPCs contain EVs with exosomal characteristics and that these vesicles can be incorporated into thyrocyte progenitors. By mass spectrometry, laminin peptides were abundantly identified in the EV preparations, probably co-sedimenting with EVs. Laminin-α1 silencing in EPC abrogated the folliculogenic effect of EVs. However, density gradient separation of EVs from laminins revealed that both EV-rich and laminin-rich fractions exhibited folliculogenic activity. In conclusion, we suggest that endothelial cells can produce EVs favouring thyrocyte organisation into follicles and lumen expansion, a mechanism promoted by laminin-α1.

Keywords: Thyroid; endothelial cells; extracellular vesicles; folliculogenesis; laminins.

Grant support

This work was supported in part by grants from the Fonds pour la Recherche Scientifique (F.R.S–FNRS, Belgium), Université catholique de Louvain (Actions de Recherche concertées), The King Baudouin Foundation.