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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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