Identification of specific somatic stem cell markers in the human endometrium and mechanisms of the bone marrow for endometrial regeneration
- Autores: Nuria López Pérez
- Directores de la Tesis: Irene Cervelló Alcaraz (dir. tes.), José Bellver Pradas (codir. tes.)
- Lectura: En la Universitat de València ( España ) en 2018
- Idioma: español
- Tribunal Calificador de la Tesis: Juan Antonio García Velasco (presid.), Xavier SantaMaría Costa (secret.), Carmen Escobedo Lucea (voc.)
- Programa de doctorado: Programa de Doctorado en Biomedicina y Biotecnología por la Universitat de València (Estudi General)
- Materias:
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- Resumen
INTRODUCTION The endometrium is a unique tissue with a high reconstitution potential during the menstrual cycle throughout the women’s reproductive life. This high regenerative potential seems to be due to the presence of somatic stem cells (SSCs) residing in the endometrial niche inside this tissue. Apart from this endogenous source, an exogenous source of stem cells composed by bone marrow-derived stem cells (BMDSCs) is postulated to exist. The endometrial contribution of bone marrow has been described in healthy and diseased women. Specifically, transplanted BMDSCs release soluble factors under tissue damage that contribute to tissue repair. To be able to differentiate both populations of stem cells, endogenous and exogenous sources, screening of specific SSC markers would allow us to locate the endogenous stem cell pool inside the tissue and, therefore, to locate the endometrial stem cell niche. However, a universal endometrial SSC marker has not been described so far.
OBJECTIVES With this background our aim was, first, to test postulated human SSC markers contributing to endometrial reconstruction in a murine model as endogenous reservoir, in order to identify a specific endometrial SSC marker. In addition, we aimed to study the role of regenerative factors released by BMDSCs as exogenous origin in women with endometrial pathologies.
MATERIALS AND METHODS A xenotransplantation model was carried out by injecting several cell subsets (according to SSC markers ICAM1, W5C5 and Side Population, SP) under the kidney capsule of immunocompromised female mice. The characterization of the newly formed tissue was performed by the expression of three endometrial markers: vimentin, cytokeratin 18 and progesterone receptor, as well as by the endometrial SSC marker Musashi-1. We also studied these stem cell populations in endometriosis samples to study its relation with the disease. In parallel, we tried to identify paracrine factors released by BMDSCs transplanted in women with Asherman’s syndrome and/or endometrial atrophy.
RESULTS AND DISCUSSION For the stem cell markers’ part, we obtained that positive cells for W5C5 and ICAM1 need the supplementation with total endometrial cells as support or niche-like cells to improve the reconstitution efficiency, probably mimicking the endometrial stem cell niche and promoting the undifferentiated state. Moreover, the Side Population is a heterogeneous population that would harbor a stem cell population in human endometrium, supported by the high regeneration capability demonstrated in the animal model.
Regarding to paracrine factors involved in endometrial regeneration, we obtained that downregulated genes are implied in immune response, inflammation and apoptosis, while upregulated ones are involved in cell growth, angiogenesis, migration, differentiation and tissue repair, being midkine a good candidate as paracrine factor responsible for endometrial regeneration.
