Angiogenic properties of endometrial mesenchymal stromal cells in endothelial co-culture: an in vitro model of endometriosis

S. Canosa, Stefano Canosa, Moggio A, Aldo Moggio, A Moggio, A Brossa, Alessia Brossa, Giulia Pittatore, Pittatore G, G Pittatore, G L Marchino, Marchino Gl, Leoncini S, Silvia Leoncini, S Leoncini, Benedetto C, C Benedetto, Chiara Benedetto, Alberto Revelli, A Revelli, B Bussolati, Benedetta Bussolati
Molecular human reproduction · 2017 · vol. 23(3) , pp. 187–198 · doi:10.1093/molehr/gax006 · PMID:28158750 · W2585442116
Lab / animal OA: bronze CC0 ⤵ 15 in-corpus citations
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Endometrial mesenchymal stromal cells acquired endothelial markers and integrated into tube-like structures when co-cultured with HUVECs, demonstrating angiogenic potential affected by anti-angiogenic agents.

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Abstract

STUDY QUESTION: Can endometrial mesenchymal stromal cells (E-MSCs) differentiate into endothelial cells in an in vitro co-culture system with human umbilical vein endothelial cells (HUVECs)? SUMMARY ANSWER: E-MSCs can acquire endothelial markers and function in a direct co-culture system with HUVECs. WHAT IS KNOWN ALREADY: E-MSCs have been identified in the human endometrium as well as in endometriotic lesions. E-MSCs appear to be involved in formation of the endometrial stromal vascular tissue and the support of tissue growth and vascularization. The use of anti-angiogenic drugs appears as a possible therapeutic strategy against endometriosis. STUDY DESIGN, SIZE, DURATION: This is an in vitro study comprising patients receiving surgical treatment of ovarian endometriosis (n = 9). PARTICIPANTS/MATERIALS, SETTING, METHODS: E-MSCs were isolated from eutopic and ectopic endometrial tissue and were characterized for the expression of mesenchymal and endothelial markers by FACS analysis and Real-Time PCR. CD31 acquisition was evaluated by FACS analysis and immunofluorescence after a 48 h-direct co-culture with green fluorescent protein +-HUVECs. A tube-forming assay was set up in order to analyze the functional potential of their interaction. Finally, co-cultures were treated with the anti-angiogenic agent Cabergoline. MAIN RESULTS AND THE ROLE OF CHANCE: A subpopulation of E-MSCs acquired CD31 expression and integrated into tube-like structures when directly in contact with HUVECs, as observed by both FACS analysis and immunofluorescence. The isolation of CD31+ E-MSCs revealed significant increases in CD31, vascular endothelial growth factor receptor 2, TEK receptor tyrosine kinase and vascular endothelial-Cadherin mRNA expression levels with respect to basal and to CD31neg cells (P < 0.05). On the other hand, the expression of mesenchymal genes such as c-Myc, Vimentin, neuronal-Cadherin and sushi domain containing 2 remained unchanged. Cabergoline treatment induced a significant reduction of the E-MSC angiogenic potential (P < 0.05 versus control). LARGE SCALE DATA: Not applicable. LIMITATIONS, REASONS FOR CAUTION: Further studies are necessary to investigate the cellular and molecular mechanisms underlying the endothelial cell differentiation. WIDER IMPLICATIONS OF THE FINDINGS: E-MSCs may undergo endothelial differentiation, and be potentially involved in the development of endometriotic implants. Cell culture systems that more closely mimic the cellular complexity typical of endometriotic tissues in vivo are required to develop novel strategies for treatment. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the 'Research Fund ex-60%', University of Turin, Turin, Italy. All authors declare that their participation in the study did not involve actual or potential conflicts of interests.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Mesenchymal Stem Cells Models, Biological Models, Biological Neovascularization, Pathologic Angiogenesis Inhibitors Angiogenesis Inhibitors Angiogenesis Inhibitors Biomarkers Biomarkers Biomarkers Cabergoline Cabergoline Cadherins Cadherins Cadherins Cadherins Cell Communication Cell Communication Cell Communication

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Papers in the corpus that this work cites (lower rings, blue) and that cite this one (upper rings, green). Dot size scales with the paper's in-corpus citation count — bigger dot = more influential within the endo/adeno field. Click a dot to open that paper. Outer rings show 2-hop neighbours — papers reached through the immediate citers/citees. [ collapse to 1-hop ]

References (47)

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