Murine embryos exposed to human endometrial MSCs-derived extracellular vesicles exhibit higher VEGF/PDGF AA release, increased blastomere count and hatching rates

Endometrial Mesenchymal Stromal Cells (endMSCs) are multipotent cells with immunomodulatory and pro-regenerative activity which is mainly mediated by a paracrine effect. The exosomes released by MSCs have become a promising therapeutic tool for the treatment of immune-mediated diseases. More specifi...

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Detalhes bibliográficos
Autores: Blazquez, Rebeca, Sánchez-Margallo, Francisco Miguel, Alvarez, Veronica, Matilla, Elvira, Hernandez, Nuria, Marinaro, Federica, Gomez-Serrano, Maria, Jorge, Inmaculada, Casado, Javier G., Macias-Garcia, Beatriz
Tipo de documento: artigo
Data de publicação:2018
País:España
Recursos:Instituto de Salud Carlos III (ISCIII)
Repositório:Repisalud
Idioma:inglês
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/6675
Acesso em linha:http://hdl.handle.net/20.500.12105/6675
Access Level:Acceso aberto
Palavra-chave:ENDOTHELIAL GROWTH-FACTOR
MESENCHYMAL STEM-CELLS
IN-VITRO
CULTURE-MEDIUM
MOUSE EMBRYO
AVIAN EMBRYO
IMPLANTATION
EXOSOMES
ANGIOGENESIS
PDGF
Descrição
Resumo:Endometrial Mesenchymal Stromal Cells (endMSCs) are multipotent cells with immunomodulatory and pro-regenerative activity which is mainly mediated by a paracrine effect. The exosomes released by MSCs have become a promising therapeutic tool for the treatment of immune-mediated diseases. More specifically, extracellular vesicles derived from endMSCs (EV-endMSCs) have demonstrated a cardioprotective effect through the release of anti-apoptotic and pro-angiogenic factors. Here we hypothesize that EV-endMSCs may be used as a co-adjuvant to improve in vitro fertilization outcomes and embryo quality. Firstly, endMSCs and EV-endMSCs were isolated and phenotypically characterized for in vitro assays. Then, in vitro studies were performed on murine embryos co-cultured with EV-endMSCs at different concentrations. Our results firstly demonstrated a significant increase on the total blastomere count of expanded murine blastocysts. Moreover, EV-endMSCs triggered the release of pro-angiogenic molecules from embryos demonstrating an EV-endMSCs concentration-dependent increase of VEGF and PDGF-AA. The release of VEGF and PDGF-AA by the embryos may indicate that the beneficial effect of EV-endMSCs could be mediating not only an increase in the blastocyst's total cell number, but also may promote endometrial angiogenesis, vascularization, differentiation and tissue remodeling. In summary, these results could be relevant for assisted reproduction being the first report describing the beneficial effect of human EV-endMSCs on embryo development.