Bovine endometrial MSC : mesenchymal to epithelial transition during luteolysis and tropism to implantation niche for immunomodulation
Calle Arias, Alexandra (Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (Espanya). Departamento de Reproducción Animal)
López-Martín, Soraya (UAM. Departamento de Biología Molecular)
Monguió-Tortajada, Marta (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Borràs i Serres, Francesc Enric (Universitat Autònoma de Barcelona. Departament de Biologia Cel·lular, de Fisiologia i d'Immunologia)
Yáñez-Mó, María (Instituto de Investigación Hospital Universitario de la Princesa)
Ramírez de Paz, Miguel Ángel (Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria (Espanya). Departamento de Reproducción Animal)

Fecha:	2019
Resumen:	The uterus is a histologically dynamic organ, and the mechanisms coordinating its regeneration during the oestrous cycle and implantation are poorly understood. The aim of this study was to isolate, immortalize and characterize bovine endometrial mesenchymal stem cell (eMSC) lines from different oestrous cycle stages (embryo in the oviduct, embryo in the uterus or absence of embryo) and examine their migratory and immunomodulatory properties in an inflammatory or implantation-like environment, as well as possible changes in cell transdifferentiation. eMSCs were isolated and analysed in terms of morphological features, expression of cell surface and intracellular markers of pluripotency, inmunocytochemical analyses, alkaline phosphatase activity, proliferation and osteogenic or chondrogenic differentiation capacities, as well as their ability to migrate in response to inflammatory (TNF-α or IL-1β) or implantation (IFN-τ) cytokines and their immunomodulatory effect in the proliferation of T cells. All eMSCs showed MSC properties such as adherence to plastic, high proliferative capacity, expression of CD44 and vimentin, undetectable expression of CD34 or MHCII, positivity for Pou5F1 and alkaline phosphatase activity. In the absence of an embryo, eMSC showed an apparent mesenchymal to epithelial transition state. eMSC during the entire oestrous cycle differentiated to osteogenic or chondrogenic lineages, showed the ability to suppress T cell proliferation and showed migratory capacity towards pro-inflammatory signal, while responded with a block in their migration to the embryo-derived pregnancy signal. This study describes for the first time the isolation, immortalization and characterization of bovine mesenchymal stem cell lines from different oestrous cycle stages, with a clear mesenchymal pattern and immunomodulatory properties. Our study also reports that the migratory capacity of the eMSC was increased towards an inflammatory niche but was reduced in response to the expression of implantation cytokine by the embryo. The combination of both signals (pro-inflammatory and implantation) would ensure the retention of eMSC in case of pregnancy, to ensure the immunomodulation necessary in the mother for embryo survival. In addition, in the absence of an embryo, eMSC showed an apparent mesenchymal to epithelial transition state.
Ayudas:	Ministerio de Economía y Competitividad AGL2015-70140-R European Commission 731014
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Endometrial mesenchymal stem cells ; Embryo implantation ; Inflammation ; Cell migration
Publicado en:	Stem cell research & therapy, Vol. 10 (january 2019) , ISSN 1757-6512

DOI: 10.1186/s13287-018-1129-1
PMID: 30635057

12 p, 5.3 MB

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Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP)
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