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Mesenchymal stem cells from different sources and their derived exosomes: A pre-clinical perspective

World Journal of Stem Cells 2020年第2期12卷 100-109页

作者： María álvarez-Viejo Unidad de Terapia Celulary Medicina Regenerativa Servicio de Hematologíay Hemoterapia Hospital Universitario Central de Asturias Plataforma de Terapias Avanzadas Instituto de Investigación Sanitaria del Principado de Asturias

Since the introduction of cell therapy as a strategy for the treatment of many diseases,mesenchymal stem cells have emerged as ideal candidates,yet the underlying mechanisms of their beneficial effects are only partially understood.At the start of the 21st century,a paracrine effect was proposed as a mechanism of tissue repair by these cells.In addition,a role was suggested for a heterogeneous population of extracellular vesicles in cell-to-cell communication.Some of these vesicles including exosomes have been isolated from most fluids and cells,as well as from supernatants of in vitro cell cultures.Recent research in the field of regenerative medicine suggests that exosomes derived from mesenchymal stem cells could be a powerful new therapeutic tool.This review examines the therapeutic potential of these exosomes obtained from the sources most used in cell therapy:bone marrow,adipose tissue,and umbilical cord.

关键词： Mesenchymal stem cells Exosomes Cellular therapy

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IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

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International Journal of Oral Science 2020年第1期12卷 31-39页

作者： Angustias Page Ana Bravo Cristian Suarez-Cabrera Raquel Sanchez-Baltasar Marta Oteo Miguel Angel Morcillo MLlanos Casanova Jose CSegovia Manuel Navarro Angel Ramirez Molecular Oncology Unit.Centro de Investigaciones Energéticas Medioambientales y Tecnológicas(CIEMAT)MadridSpain Instituto de Investigación 12 de Octubre i+12 MadridSpain Centro de Investigación Biomédica en Red de Cáncer(CIBERONC) MadridSpain department of Anatomy Animal Production and Veterinary Clinical SciencesLaboratory of Pathology Phenotyping of Genetically Engineered MiceFaculty of Veterinary MedicineUniversity of Santiago de CompostelaLugoSpain Biomedical Applications and Pharmacokinetics Unit Centro de Investigaciones EnergéticasMedioambientales y Tecnológicas(CIEMAT)MadridSpain Hematopoietic Innovative Therapies Division.Centro de Investigaciones Energéticas Medioambientales y Tecnológicas(CIEMAT).Centro de Investigación Biomédica en Red de Enfermedades Raras(CIBERER)MadridSpain Unidad Mixta de terapias avanzadas Fundación Instituto de Investigaciones Sanitarias Fundación Jiménez DíazMadridSpain

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog,MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ(a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and mi RNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins(p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity.These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.

关键词： IKKβ tumour suppressor

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Pathophysiological 角色和在糖尿病的 nephropathy 的发炎的治疗学的含意

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World Journal of Diabetes 2012年第1期3卷 7-18页

作者： desirée Luis-Rodríguez Alberto Martínez-Castelao José Luis Górriz Fernando de lvaro Juan F Navarro-González Grupo Espaol para el Estudio de la Nefropatía Diabética (GEENDIAB) Spain Nephrology Service and Research Unit University Hospital Nuestra Seora de Candelaria 38010 Santa Cruz de Tenerife Spain Nephrology Service Bellvitge University Hospital 08907 L’Hospitalet de Llobregat Spain Nephrology Service University Hospital Dr. Peset 46017 Valencia Spain Nephrology Service University Hospital Infanta Sofía 28702 Madrid Sapin

Diabetes mellitus and its complications are becoming one of the most important health problems in the world. Diabetic nephropathy is now the main cause of end-stage renal disease. The mechanisms leading tothe development and progression of renal injury are not well known. Therefore, it is very important to f ind new pathogenic pathways to provide opportunities for early diagnosis and targets for novel treatments. At the present time, we know that activation of innate immunity with development of a chronic low grade inflammatory response is a recognized factor in the pathogenesis of diabetic nephropathy. Numerous experimental and clinical studies have shown the participation of different inflammatory molecules and pathways in the pathophysiology of this complication.

关键词： Diabetes Diabetic nephropathy Innate immunity Inflammation Renal failure

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WJD 5^(th) Anniversary Special Issues(2): Type 2 diabetes Inflammation in diabetic kidney disease

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World Journal of Diabetes 2014年第4期5卷 431-443页

作者： Patricia M García-García María A Getino-Melian Virginia Domínguez-Pimentel Juan F Navarro-Gonzalez Nephrology Service and Research Unit University Hospital Nuestra Se?ora de Candelaria 38010 Santa Cruz de Tenerife Spain Spanish National Coordinator of GEENDIAB (Grupo Espa ol para el Estudio de la Nefropatía Di-abética) (RedInRen 12/0021/0019 Instituto de Salud Carlos IIIMinisterio de Economía y Competitividad) 38010 Santa Cruz de Tenerife Spain

Diabetes mellitus entails significant health problems worldwide.The pathogenesis of diabetes is multifactorial,resulting from interactions of both genetic and environmental factors that trigger a complex network of pathophysiological events,with metabolic and hemodynamic alterations.In this context,inflammation has emerged as a key pathophysiology mechanism.New pathogenic pathways will provide targets for prevention or future treatments.This review will focus on the implications of inflammation in diabetes mellitus,with special attention to inflammatory cytokines.

关键词： Diabetes Diabetic nephropathy Diabetic kidney disease Inflammation Cytokines Oxidative stress

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