"Endometrial-Mesenchymal Stem Cells: involvement and therapeutic implications in endometriosis"

Endometriosis is a common gynecologic disorder characterized by the growth of endometrial tissue outside the uterine cavity, leading to pelvic pain and infertility. Endometrial lesions are characterized by extensive angiogenesis, which has recently been investigated as a potential target for a therapeutic approach. Endometrial-Mesenchymal Stromal Cells (E-MSCs) are responsible for the spreading of endometrial lesions and for their angiogenesis, by differentiating and acquiring endothelial features. In this work, we aimed at investigating whether Quinagolide, a D2 Dopamine Receptor (D2DR) agonist, may affect E-MSCs pro-angiogenic and invasive features and the mechanisms involved. We first generated and characterized E-MSC from ovarian and peritoneal lesions. E-MSCs were positive for mesenchymal markers, highlighting a heterogeneous composition of stromal fibroblasts and mesenchymal stem cells, and expressed the D2DR. We first tested the effect of Quinagolide in a model of mesenchymal-to-endothelial transition in which E-MSCs co-cultured with HUVECs GFP+ differentiate into endothelial cells. Cytofluorimetric analysis revealed that Quinagolide treatment on co-cultures had a role in reducing the mesenchymal-to-endothelial transition. In addition, Quinagolide affected the invasive ability of E-MSCs in a model of 3D Matrigel invasion. Quinagolide did not influence cellular processes other than invasion, such as proliferation and apoptosis. Finally, the modulation of AKT pathway in untreated and Quinagolide-treated cells was investigated as a potential regulator of endometriotic behaviors, showing that Quinagolide induced its downregulation. All together, these evidences show that Quinagolide, by acting on both invasion and endothelial differentiation of E-MSCs, might represent a potential relevant molecule for the therapy of endometriosis.