https://hdl.handle.net/10481/24518 2026-04-11T20:59:51Z https://hdl.handle.net/10481/111367 Characterization of mesenchymal stem/stromal cells with lymphoid tissue organizer cell potential in tonsils from children Prados, Alejandro; Muñoz-Fernández, Raquel; Fernández-Rubio, Pablo; García Olivares, Enrique Fernando Lymphoid tissue organizer (LTo) cells, identified in mouse and human embryos, are thought to be precursors of stromal cells in secondary lymphoid organs. Whether LTo cells are present in human adults, however remains unknown. We obtained 15 stromal cell lines from tonsils from children who underwent tonsillectomy, and studied the antigen phenotype of these tonsil stromal cell (TSC) lines by flow cytometry and RT-PCR. Cell lines met the minimal criteria proposed by the International Society for Cellular Therapy to define human mesenchymal stem/stromal cells (MSCs): plastic-adherent capacity; expression of CD73, CD90 and CD105, lack of CD45, CD19 and HLA-DR; and capacity to differentiate into adipocytes, osteoblasts and chondrocytes. Furthermore, our TSC lines exhibited an antigen phenotype and functional characteristics very similar to those seen in murine embryo LTo cells: they expressed chemokines CCL19, CCL21 and CXCL13, cytokines TRANCE and IL-7, and adhesion molecules ICAM-1, mucosal addressin cell adhesion molecule (MadCAM)-1 and VCAM-1. The expression of LTo cell- associated markers and functions were upregulated by lymphotoxin (LT)α1β2 and TNF, two cytokines involved in the development and maturation of secondary lymphoid tis- sues. Our results show that TSCs are tonsil MSCs that differentiate into LTo-like cells in response to the effects of these cytokines. https://hdl.handle.net/10481/111354 Mesenchymal cells in inflammation, immunity and cancer Koliaraki, Vasiliki; Prados, Alejandro; Armaka, Marietta; Kollias, George Mesenchymal cells are mesoderm-derived stromal cells that are best known for providing structural support to organs, synthesizing and remodeling the extracellular matrix (ECM) and regulating development, homeostasis and repair of tissues. Recent detailed mechanistic insights into the biology of fibroblastic mesenchymal cells have revealed they are also significantly involved in immune regulation, stem cell maintenance and blood vessel function. It is now becoming evident that these functions, when defective, drive the development of complex diseases, such as various immunopathologies, chronic inflammatory disease, tissue fibrosis and cancer. Here, we provide a concise overview of the contextual contribution of fibroblastic mesenchymal cells in physiology and disease and bring into focus emerging evidence for both their heterogeneity at the single-cell level and their tissue-specific, spatiotemporal functional diversity. https://hdl.handle.net/10481/111342 Human decidual stromal cells secrete C-X-C motif chemokine 13, express B cell-activating factor and rescue B lymphocytes from apoptosis: distinctive characteristics of follicular dendritic cells Muñoz-Fernández, Raquel; Prados, Alejandro; Leno-Durán, Esther; Blazquez, A.; García-Fernández, J.R.; Ortiz-Ferrón, Gustavo; García Olivares, Enrique Fernando BACKGROUND: Decidual stromal cells (DSCs) have classically been considered fibroblastic cells, although their function, cell lineage and origin are not fully understood. We previously demonstrated that human DSCs showed similarities with follicular dendritic cells (FDCs): DSCs expressed FDC-associated antigens, both types of cells are contractile and both are related to mesenchymal stem cells (MSCs). To further characterize DSCs, we investigated whether DSCs and FDCs share any distinctive phenotypical and functional characteristics. METHODS: Human FDC lines were obtained from tonsillectomy samples, human DSC lines from elective termination of pregnancy samples and human MSC lines from bone marrow aspirates. We isolated DSC, FDC and MSC lines and compared their characteristics with flow cytometry and enzyme-linked immunosorbent assay. Cell lines were cultured with tumour necrosis factor (TNF) and lymphotoxin LT alpha1\beta2, cytokines involved in FDC differentiation. Cell lines were also differentiated in culture after exposure to progesterone and cAMP. RESULTS: Like MSCs, DSCs and FDCs expressed MSC-associated antigens (CD10, CD29, CD54, CD73, CD106, a-smooth muscle actin and STRO-1) and lacked CD45 expression, and all three types of cell line showed increased expression of CD54 (ICAM-1) and CD106 (VCAM-1) when cultured TNF and LT alpha 1 \ beta 2. DSCs and FDCs, however, exhibited characteristics not observed in MSCs: DSCs expressed FDC-associated antigens CD14, CD21 and CD23, B cell-activating factor and secreted C-X-C motif chemokine 13. Moreover, DSC lines but not MSC lines inhibited the spontaneous apoptosis of B lymphocytes, a typical functional attribute of FDC. During culture with progesterone and CAMP, FDCs, like DSCs but in contrast to MSCs, changed their morphology from a fibroblastic to a rounder shape, and cells secreted prolactin. CONCLUSIONS: Our results suggest that DSCs and FDCs share a common precursor in MSCs but this precursor acquires new capacities when it homes to peripheral tissues. We discuss these shared properties in the context of immune-endocrine regulation during pregnancy. https://hdl.handle.net/10481/111338 Apoptotic DC-SIGN+ cells in normal human decidua Tirado-González, Irene; Muñoz-Fernández, Raquel; Prados, Alejandro; Leno-Durán, Esther; Martin, Francisco; Abadía Molina, Ana Clara; García Olivares, Enrique Fernando Background: Normal pregnancy and spontaneous abortion in humans and mice are associated with immune responses. The decidua harbors dendritic cells identifiable in humans by their expression of DC-SIGN. Because dendritic cells are essential for immune response regulation, decidual DC-SIGN+ cells may play a role in normal or pathological pregnancy outcomes. Previous reports suggested that DC interact with NK cells in decidua, although the functional significance of this phenomenon remains unknown. Objective: We studied the presence of conjugates of DC-SIGN+ cells with CD56+ NK cells in normal human decidua. Methods: Conjugates of DC-SIGN+ cells with CD56+ NK cells were studied in leukocyte suspensions of normal human decidua (6-11 weeks) by flow cytometry and confocal microscopy. The presence of apoptotic cells was determined by the TUNEL assay, incubation with annexin V and confocal microscopy in decidual leukocyte suspensions and by the TUNEL assay in decidual sections. Results: We observed conjugates of decidual DC-SIGN+ cells with CD56+ NK cells (40.2 ± 26.1% of all the DC-SIGN+ cells by flow cytometry and 52.3 ± 10.2% by confocal microscopy). We also found that a proportion of DC-SIGN+ cells were in apoptosis, since they were TUNEL+ (40.2 ± 7.2% of all DC-SIGN+ cells in decidual sections) and annexin V+ (34.4 ± 15.2% in leukocyte suspensions). And sorted DC-SIGN+ cells had multilobulated nuclei. Conclusions: The conjugates of decidual DC-SIGN+ cells with CD56+ NK cells strongly suggest that these latter cells induce apoptosis in DC-SIGN+ cells during normal pregnancy. We discuss this possibility in the context of maternal-fetal tolerance. This work was supported by grants from the Fondo de Investigación Sanitaria, Ministry of Health of Spain (PS09/00339), and from the Fundación Progreso y Salud (TCRM 0010/2006). https://hdl.handle.net/10481/108908 Gut feelings–the gut microbiome as a regulator of mental health in polycystic ovary syndrome Arffman Riikka K., /; Folch, Bárbara; Leonés-Baños, Irene; Altmae, Signe Importance: Polycystic ovary syndrome (PCOS) is a common endocrine disorder associated with reproductive, metabolic, and mental health comorbidities. The exact mechanisms of PCOS-related psychological distress and the role of the microbiome in the process remain unclear. Objective: To systematically review the current literature on the gut microbiome’s association with mental health in women with PCOS and to review the possible mechanisms. Evidence Review: A comprehensive literature search across the PubMed database until July 2025. Studies were included if they met the following criteria: observational/intervention studies; assessing microbiome through 16S ribosomal ribonucleic acid amplicon/ 16S ribosomal ribonucleic acid gene sequencing/metagenomics; comparing microbiome between women with and without PCOS; published from 2007 until 2025, and articles available online. The exclusion criteria were: language other than English or Spanish; reviews; abstracts/posters; case reports; full text not available, and duplicates. Two independent reviewers screened all titles and abstracts to determine eligibility, and discrepancies were resolved through discussion. The methodological quality and the potential risk of bias were assessed following the Joanna Briggs Institute Critical Appraisal Checklist for Case–Control Studies. Findings: Atotal of 159 studies were identified and screened fortitle, abstract, and fulltext. Eightstudiesmetthe criteria (2 rodent, 6 human studies). The quality assessmentindicated that half ofthe studies(4/8) presented a highrisk of bias.Regardless ofthe limitednumber ofstudies and the low quality scores, all the studies highlighted the association of the gut microbiome in PCOS with mental health problems. Conclusions and relevance: Our review provides the first summary of the studies performed to date on the gut–brain axis in PCOS. Our review highlights that the current state of the research is rather preliminary, and the existing studies possess various limitations and often lack rigorous study design. Nevertheless, all the studies indicated an association between changes in gut microbiome and mental health indicators in PCOS. We also noted a consistent increase in Gram-negative bacteria in women with PCOS and mental health issues. More research is needed on humans with a bigger sample size, different ethnicities, and wider age groups to clarify the microbial patterns involved, and in parallel, the field should move from descriptive studies to mechanistic approaches. (Fertil Steril® 2025;124:931–47. ©2025 by American Society for Reproductive Medicine.)