Person: Portolés Pérez, María Teresa
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First Name
María Teresa
Last Name
Portolés Pérez
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Químicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
Identifiers
20 results
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Item Effects of ipriflavone-loaded mesoporous nanospheres on the differentiation of endothelial cells and their modulation by macrophages.(Nanomaterials, 2021) Casarrubios Molina, Laura; Polo Montalvo, Alberto; Serrano, María Concepción; Feito Castellano, María José; Vallet Regí, María Dulce Nombre; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaAngiogenic biomaterials for bone repair are being designed to promote vascularization and optimize tissue regeneration. The use of nanoparticles of bioactive materials loaded with different drugs represents an interesting strategy to stimulate osteogenesis and angiogenesis and to inhibit bone resorption. Ipriflavone (IP) prevents osteoporosis by inhibiting osteoclast activity and promoting preosteoblast differentiation into mature osteoblasts. Since endothelial progenitor cells (EPCs) are involved in the formation of blood vessels which are necessary for tissue regeneration, the isolation and characterization of porcine EPCs have been carried out in this work to evaluate the in vitro effects of unloaded (NanoMBGs) and IP-loaded nanospheres (NanoMBG-IPs) designed to stimulate osteogenesis. Because different signals between vascular and nonvascular cells are also essential to initiate angiogenic events, the potential modulating role of macrophages has been also evaluated by studying the expression of vascular endothelial growth factor receptor 2 (VEFGR2) as a specific marker for EPC differentiation under different culture conditions: a) EPCs in monoculture treated with NanoMBGs or NanoMBG-IPs, b) EPCs treated with conditioned media from basal, proinflammatory M1 and reparative M2 macrophages previously treated with NanoMBGs or NanoMBG-IPs, c) EPCs cocultured with macrophages in the presence of NanoMBGs or NanoMBG-IPs, and d) EPCs cocultured with M2d angiogenic macrophages. Moreover, the endocytic mechanisms by which these nanospheres are incorporated by EPCs have been identified by using six endocytosis inhibitors (i.e. wortmannin, genistein, cytochalasin B, cytochalasin D, phenylarsine oxide and chlorpromazine) and before the addition of NanoMBGs labeled with fluorescein isothiocyanate. The results evidence the great potential of both NanoMBGs and NanoMBG-IPs to enhance VEFGR2 expression, directly related to angiogenesis, after intracellular incorporation by EPCs through different endocytic mechanisms including clathrin-dependent endocytosis, as the main entry mechanism, but also phagocytosis and caveolae-mediated uptake. The treatment of EPCs with culture media from basal, M1 and M2 macrophages and the development of cocultures of EPCs with macrophages in the absence and presence of these nanomaterials have also confirmed the maintenance of their angiogenic effect on EPCs even in the presence of phagocytic cells.- Project number: PIMCD197/23-24
Item Estrategias docentes innovadoras para el estudio de las interrelaciones metabólicas entre órganos y tejidos especializados y su papel clave en diferentes estados fisiopatológicos(2024) Portolés Pérez, María Teresa; Arriaga Muñoz, Katherine Margot; Baena Montero, Lydia; Burillo Barbudo, Carla; Casarrubios Molina, Laura; Castillo San Martin, Claudia; Cicuéndez Maroto, Mónica; Del Río Rodríguez, Sandra; Del Valle Díaz, Aitana; Delgado Lázaro, Irene; Echaide Torreguitar, Mercedes; Fernández Cerrada, Candela; Fernández Herrero, Andrea María; Fernández Vicente, Raquel; Frutos Gómez, Adriana; Fuerte Sánchez, Elena; García Molina, Selena; Gómez Miguel, Begoña; González García, Sonia; Gutiérrez Rodríguez, Diego; Hornero Muñoz, María; Inche-Durand, Raffaella Lorena; León Martín, Prado; Mallavía Estepa, Carmen María; Marín Torralba, Raúl; Martínez Collado, Adriana; Molina López, David Martín; Moragrega Molina, Daniel; Rodríguez Márquez, Guillermo; Rodríguez Muñoz, David; Rodrígez-Palanca Coloma, Candela; Ruiz Josa, Marcos; Saborido Modia, Ana Isolina; Sánchez Fernández, Diego; Varea López Murillas, María Lourdes; Portolés Pérez, María TeresaEl objetivo principal del proyecto es facilitar el estudio del metabolismo, su regulación y las interrelaciones entre órganos y tejidos con distintos perfiles metabólicos, destacando su importancia en diversos estados fisiopatológicos. El proyecto pretende además poner de manifiesto la importancia de estos conocimientos para poder desarrollar proyectos de investigación en diferentes áreas. Con este objetivo, los estudiantes de los cinco grupos de primero de Grado en Biología, tutorizados por M Teresa Portolés (responsable del proyecto), Begoña Gómez-Miguel, Ana Saborido y Mercedes Echaide, profesoras que imparten Metabolismo en la asignatura de Bioquímica, han realizado las actividades indicadas a continuación, organizados en equipos de trabajo centrados en órganos y tejidos clave como cerebro, hígado, músculo, tejido adiposo y glóbulos rojos. - Elaboración de preguntas de examen, fijando la atención en los aspectos más importantes al finalizar el estudio de cada tema. - Realización de infografías expuestas en la Facultad de Ciencias Biológicas del 13 al 17 de mayo, para representar de forma clara, concisa y atractiva las características metabólicas de tipos celulares especializados y sus interrelaciones, facilitando su comprensión y estudio. - Elaboración de un mapa integrador interactivo del metabolismo en las aulas de informática de la Facultad de Ciencias Biológicas con la pizarra digital interactiva, destacando la interconexión de las diferentes rutas metabólicas en la que se basa el funcionamiento del organismo. Laura Casarrubios (Doctora en Biología) ha participado preparando dos vídeos explicativos de los programas Miro y BioRender. - Asistencia a charlas impartidas por las profesoras del proyecto enfocadas en sus proyectos de investigación y con la participación de Mónica Cicuéndez (PAD) experta en Metabolómica, para transmitir a los estudiantes la importancia del estudio del metabolismo en el desarrollo de actividades investigadoras en diferentes áreas. El proyecto ha contado con la participación de Lourdes Varea (Secretaria Administrativa) para la organización de los listados de los diferentes equipos y otras tareas administrativas, así como con numerosos estudiantes colaboradores de cursos anteriores que han aconsejado a los nuevos estudiantes en las actividades realizadas. El proyecto es interfacultativo e interdepartamental, ya que los componentes del equipo pertenecen a las Facultades de Ciencias Químicas, Ciencias Biológicas y Farmacia, y a los Departamentos de Bioquímica y Biología Molecular y Química en Ciencias Farmacéuticas. El equipo cuenta con 5 miembros PDI (1 Catedrática de Universidad, 3 Profesoras Titulares de Universidad y 1 Profesora Ayudante Doctor), 2 miembros PAS y estudiantes de cursos anteriores. El elevado número de estudiantes (alrededor de 400) que han desarrollado las diferentes actividades, pone de manifiesto el entusiasmo del alumnado y deja constancia de la motivación y el interés que el proyecto ha despertado en los estudiantes de primero de Grado en Biología. Item Response of RAW 264.7 and J774A.1 macrophages to particles and nanoparticles of a mesoporous bioactive glass: A comparative study(Colloids and Surfaces B: Biointerfaces, 2021) Feito Castellano, María José; Casarrubios Molina, Laura; Oñaderra Sánchez, Mercedes; Gómez Duro, M.; Arribas, P.; Polo Montalvo, A.; Arcos Navarrete, Daniel; Portolés Pérez, María Teresa; Vallet Regí, María Dulce NombreMesoporous bioactive glasses (MBGs) are bioceramics designed to induce bone tissue regeneration and very useful materials with the ability to act as drug delivery systems. MBGs can be implanted in contact with bone tissue in different ways, as particulate material, in 3D scaffolds or as nanospheres. In this work, we assessed the effects of particles of mesoporous bioactive glass MBG-75S and mesoporous nanospheres NanoMBG-75S on RAW 264.7 and J774A.1 macrophages, which present different sensitivity and are considered as ideal models for the study of innate immune response. After evaluating several cellular parameters (morphology, size, complexity, proliferation, cell cycle and intracellular content of reactive oxygen species), the action MBG-75S particles and NanoMBG-75S on the polarization of these macrophages towards the pro-inflammatory (M1) or reparative (M2) phenotype was determined by the expression of specific M1 (CD80) and M2 (CD206, CD163) markers. We previously measured the adsorption of albumin and fibrinogen on MBG-75S particles and the production of pro-inflammatory cytokines as TNF-α and IL-6 by macrophages in response to these particles. This comparative study demonstrates that particles of mesoporous bioactive glass MBG-75S and mesoporous nanospheres NanoMBG-75S allow the appropriated development and function of RAW 264.7 and J774A.1 macrophages and do not induce polarization towards the M1 pro-inflammatory phenotype. Therefore, considering that these mesoporous biomaterials offer the possibility of loading drugs into their pores, the results obtained indicate their high potential for use as drug-delivery systems in bone repair and osteoporosis treatments without triggering an adverse inflammatory response.Item Osteoimmune Properties of Mesoporous Bioactive Nanospheres: A Study on T Helper Lymphocytes(Nanomaterials, 2023) Casarrubios Molina, Laura; Cicuéndez Maroto, Mónica; Vallet Regí, María Dulce Nombre; Portolés Pérez, María Teresa; Arcos Navarrete, Daniel; Feito Castellano, María JoséBioactive mesoporous glass nanospheres (nanoMBGs) charged with antiosteoporotic drugs have great potential for the treatment of osteoporosis and fracture prevention. In this scenario, cells of the immune system are essential both in the development of disease and in their potential to stimulate therapeutic effects. In the present work, we hypothesize that nanoMBGs loaded with ipriflavone can exert a positive osteoimmune effect. With this objective, we assessed the effects of non-loaded and ipriflavone-loaded nanoparticles (nanoMBGs and nanoMBG-IPs, respectively) on CD4+ Th2 lymphocytes because this kind of cell is implicated in the inhibition of osseous loss by reducing the RANKL/OPG relationship through the secretion of cytokines. The results indicate that nanoMBGs enter efficiently in CD4+ Th2 lymphocytes, mainly through phagocytosis and clathrindependent mechanisms, without affecting the function of these T cells or inducing inflammatory mediators or oxidative stress, thus maintaining the reparative Th2 phenotype. Furthermore, the incorporation of the anti-osteoporotic drug ipriflavone reduces the potential unwanted inflammatory response by decreasing the presence of ROS and stimulating intracellular anti-inflammatory cytokine release like IL-4. These results evidenced that nanoMBG loaded with ipriflavone exerts a positive osteoimmune effect.Item Osteogenic-angiogenic coupled response of cobalt-containing mesoporous bioactive glasses in vivo(Acta Biomaterialia, 2024) Jiménez Holguín, Javier; Lozano Borregón, Daniel; Saiz-Pardo Sanz, Melchor; Pablo, David de; Ortega, Luis ; Enciso, Silvia; Fernandez Tome, Blanca; Díaz-Güemes, Idoia; Sanchez Margallo, Francisco Miguel; Portolés Pérez, María Teresa; Arcos Navarrete, DanielThe incorporation of cobalt ions into the composition of bioactive glasses has emerged as a strategy of interest for bone regeneration purposes. In the present work, we have designed a set of bioactive mesoporous glasses SiO2 -CaO-P2 O5 -CoO (Co-MBGs) with different amounts of cobalt. The physicochemi- cal changes introduced by the Co2 + ion, the in vitro effects of Co-MBGs on preosteoblasts and endothelial cells and their in vivo behaviour using them as bone grafts in a sheep model were studied. The results show that Co2 + ions neither destroy mesoporous ordering nor inhibit in vitro bioactive behaviour, ex- erting a dual role as network former and modifier for CoO concentrations above 3 % mol. On the other hand, the activity of Co-MBGs on MC3T3-E1 preosteoblasts and HUVEC vascular endothelial cells is de- pendent on the concentration of CoO present in the glass. For low Co-MBGs concentrations (1mg/ml) cell viability is not affected, while the expression of osteogenic (ALP, RUNX2 and OC) and angiogenic (VEGF) genes is stimulated. For Co-MBGs concentration of 5 mg/ml, cell viability decreases as a function of the CoO content. In vivo studies show that the incorporation of Co2 + ions to the MBGs improves the bone regeneration activity of these materials, despite the deleterious effect that this ion has on bone-forming cells for any of the Co-MBG compositions studied. This contradictory effect is explained by the marked increase in angiogenesis that takes place inside the bone defect, leadingItem Effects of graphene oxide and reduced graphene oxide nanomaterials on porcine endothelial progenitor cells(Nanoscale, 2023) Polo Montalvo, Alberto; Cicuéndez Maroto, Mónica; Casarrubios Molina, Laura; Barroca, Natalia; Silva, Daniela; Feito Castellano, María José; Díez Orejas, Rosalía María; Serrano López-Terradas, María de la Concepción; Marques, Paula; Portolés Pérez, María TeresaGraphene oxide (GO) and reduced graphene oxide (rGO) have been widely used in the field of tissue regeneration and various biomedical applications. In order to use these nanomaterials in organisms, it is imperative to possess an understanding of their impact on different cell types. Due to the potential of these nanomaterials to enter the bloodstream, interact with the endothelium and accumulate within diverse tissues, it is highly relevant to probe them when in contact with the cellular components of the vascular system. Endothelial progenitor cells (EPCs), involved in blood vessel formation, have great potential for tissue engineering and offer great advantages to study the possible angiogenic effects of biomaterials. Vascular endothelial growth factor (VEGF) induces angiogenesis and regulates vascular permeability, mainly activating VEGFR2 on endothelial cells. The effects of GO and two types of reduced GO, obtained after vacuum-assisted thermal treatment for 15 min (rGO15) and 30 min (rGO30), on porcine endothelial progenitor cells (EPCs) functionality were assessed by analyzing the nanomaterial intracellular uptake, reactive oxygen species (ROS) production and VEGFR2 expression by EPCs. The results evidence that short annealing (15 and 30 minutes) at 200 °C of GO resulted in the mitigation of both the increased ROS production and decline in VEGFR2 expression of EPCs upon GO exposure. Interestingly, after 72 hours of exposure to rGO30, VEGFR2 was higher than in the control culture, suggesting an early angiogenic potential of rGO30. The present work reveals that discrete variations in the reduction of GO may significantly affect the response of porcine endothelial progenitor cells.Item Functionality of macrophages encapsulated in porcine decellularized adipose matrix hydrogels and interaction with Candida albicans(Biomaterials Advances, 2024) Cicuéndez Maroto, Mónica; García-Lizarribar, Andrea; Casarrubios Molina, Laura; Feito Castellano, María José; Fernández San Argimiro, Francisco Javier; García Urkia, Nerea; Murua, Olatz; Madarieta, Iratxe; Olalde, Beatriz; Díez Orejas, Rosalía María; Portolés Pérez, María TeresaExtracellular matrix hydrogels are considered one of the most suitable biomaterials for tissue regeneration due to their similarity with the extracellular microenvironment of the native tissue. Their properties are dependent on their composition, material concentration, fiber density and the fabrication approaches, among other factors. The encapsulation of immune cells in this kind of hydrogels, both in absence or presence of a pathogen, represents a promising strategy for the development of platforms that mimic healthy and infected tissues, respectively. In this work, we have encapsulated macrophages in 3D hydrogels of porcine decellularized adipose matrices (pDAMs) without and with the Candida albicans fungus, as 3D experimental models to study the macrophage immunocompetence in a closer situation to the physiological conditions and to mimic an infection scenario. Our results indicate that encapsulated macrophages preserve their functionality within these pDAM hydrogels and phagocytose live pathogens. In addition, their behavior is influenced by the hydrogel pore size, inversely related to the hydrogel concentration. Thus, larger pore size promotes the polarization of macrophages towards M2 phenotype along the time and enhances their phagocytosis capability. It is important to point out that encapsulated macrophages in absence of pathogen showed an M2 phenotype, but macrophages coencapsulated with C. albicans can switch towards an M1 inflammatory phenotype to resolve the infection, depending on the fungus quantity. The present study reveals that pDAM hydrogels preserve the macrophage plasticity, demonstrating their relevance as new models for macrophage-pathogen interaction studies that mimic an infection scenario with application in regenerative medicine research.Item Effective Actions of Ion Release from Mesoporous Bioactive Glass and Macrophage Mediators on the Differentiation of Osteoprogenitor and Endothelial Progenitor Cells(Pharmaceutics, 2021) Polo Montalvo, Alberto; Casarrubios Molina, Laura; Serrano, María Concepción; Sanvicente, Adrián; Feito Castellano, María José; Arcos Navarrete, Daniel; Portolés Pérez, María TeresaDue to their specific mesoporous structure and large surface area, mesoporous bioactive glasses (MBGs) possess both drug-delivery ability and effective ionic release to promote bone regeneration by stimulating osteogenesis and angiogenesis. Macrophages secrete mediators that can affect both processes, depending on their phenotype. In this work, the action of ion release from MBG-75S, with a molar composition of 75SiO2-20CaO-5P2O5, on osteogenesis and angiogenesis and the modulatory role of macrophages have been assessed in vitro with MC3T3-E1 pre-osteoblasts and endothelial progenitor cells (EPCs) in monoculture and in coculture with RAW 264.7 macrophages. Ca2+, phosphorous, and silicon ions released from MBG-75S were measured in the culture medium during both differentiation processes. Alkaline phosphatase activity and matrix mineralization were quantified as the key markers of osteogenic differentiation in MC3T3-E1 cells. The expression of CD31, CD34, VEGFR2, eNOS, and vWF was evaluated to characterize the EPC differentiation into mature endothelial cells. Other cellular parameters analyzed included the cell size and complexity, intracellular calcium, and intracellular content of the reactive oxygen species. The results obtained indicate that the ions released by MBG-75S promote osteogenesis and angiogenesis in vitro, evidencing a macrophage inhibitory role in these processes and demonstrating the high potential of MBG-75S for the preparation of implants for bone regeneration.Item Mesoporous Bioactive Nanoparticles for Bone Tissue Applications(International Journal of Molecular Sciences, 2023) Arcos Navarrete, Daniel; Portolés Pérez, María TeresaResearch in nanomaterials with applications in bone regeneration therapies has experienced a very significant advance with the development of bioactive mesoporous nanoparticles (MBNPs). These nanomaterials consist of small spherical particles that exhibit chemical properties and porous structures that stimulate bone tissue regeneration, since they have a composition similar to that of conventional sol–gel bioactive glasses and high specific surface area and porosity values. The rational design of mesoporosity and their ability to incorporate drugs make MBNPs an excellent tool for the treatment of bone defects, as well as the pathologies that cause them, such as osteoporosis, bone cancer, and infection, among others. Moreover, the small size of MBNPs allows them to penetrate inside the cells, provoking specific cellular responses that conventional bone grafts cannot perform. In this review, different aspects of MBNPs are comprehensively collected and discussed, including synthesis strategies, behavior as drug delivery systems, incorporation of therapeutic ions, formation of composites, specific cellular response and, finally, in vivo studies that have been performed to date .Item Mesoporous Bioactive Nanoparticles for Bone Tissue Applications(International Journal of Molecular Sciences, 2023) Arcos Navarrete, Daniel; Portolés Pérez, María TeresaResearch in nanomaterials with applications in bone regeneration therapies has experienced a very significant advance with the development of bioactive mesoporous nanoparticles (MBNPs). These nanomaterials consist of small spherical particles that exhibit chemical properties and porous structures that stimulate bone tissue regeneration, since they have a composition similar to that of conventional sol–gel bioactive glasses and high specific surface area and porosity values. The rational design of mesoporosity and their ability to incorporate drugs make MBNPs an excellent tool for the treatment of bone defects, as well as the pathologies that cause them, such as osteoporosis, bone cancer, and infection, among others. Moreover, the small size of MBNPs allows them to penetrate inside the cells, provoking specific cellular responses that conventional bone grafts cannot perform. In this review, different aspects of MBNPs are comprehensively collected and discussed, including synthesis strategies, behavior as drug delivery systems, incorporation of therapeutic ions, formation of composites, specific cellular response and, finally, in vivo studies that have been performed to date.