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Start Over Author "Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)" Journal international journal of molecular sciences Publisher mdpi ag
6 results on '"Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT)"'

1. Possible Adverse Effects of Food Additive E171 (Titanium Dioxide) Related to Particle Specific Human Toxicity, Including the Immune System

Author

Antoon Opperhuizen, Morten Poulsen, Dick T. H. M. Sijm, Hubert Dirven, Gerhard Rogler, Eric Houdeau, Nicolaj S Bischoff, Simone G. J. van Breda, David Michael Gott, Jacqueline Castenmiller, Theo M. de Kok, Henk Van Loveren, Jacco J. Briedé, Yolanda I. Chirino, Agnes G. Oomen, University of Zurich, Bischoff, Nicolaj S, School for Oncology and Developmental Biology [Maastricht] (GROW), Maastricht University [Maastricht]-Maastricht University Medical Centre (MUMC), Maastricht University [Maastricht], Netherlands Food and Consumer Product Safety Authority (NVWA), Universidad Autonoma Metropolitana - Iztapalapa, Norwegian Institute of Public Health [Oslo] (NIPH), FOOD STANDARDS AGENCY LONDON GBR, Partenaires IRSTEA, Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA)-Institut national de recherche en sciences et technologies pour l'environnement et l'agriculture (IRSTEA), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), National Institute for Public Health and the Environment [Bilthoven] (RIVM), Technical University of Denmark [Lyngby] (DTU), University hospital of Zurich [Zurich], and Office of Risk Assessment and Research of Netherlands Food and Consumer Product Safety Authority (NVWA)

Subjects
0301 basic medicine, 3 NANOSCALE, tio2 nanoparticles, 1607 Spectroscopy, 010501 environmental sciences, 01 natural sciences, in-vivo, INTESTINAL EPITHELIUM, Dietary Exposure, lcsh:Chemistry, Adverse health effect, Adverse Outcome Pathway, Medicine, Ingestion, TiO2, Coloring Agents, lcsh:QH301-705.5, Spectroscopy, Titanium, dna-damage, General Medicine, 3. Good health, Computer Science Applications, food safety, 10219 Clinic for Gastroenterology and Hepatology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, nanomaterial, 1606 Physical and Theoretical Chemistry, Risk assessment, TiO 2, food.ingredient, PIGMENT-GRADE, 1503 Catalysis, review, 610 Medicine & health, Catalysis, Inorganic Chemistry, 03 medical and health sciences, food, Immune system, mode of action, Environmental health, Toxicity Tests, 1312 Molecular Biology, 1706 Computer Science Applications, Animals, Humans, EXPOSURE, Physical and Theoretical Chemistry, Adverse effect, Molecular Biology, E171, 0105 earth and related environmental sciences, food additive, 1604 Inorganic Chemistry, business.industry, titanium dioxide, Food additive, Organic Chemistry, adverse health effects, technology, industry, and agriculture, risk-assessment, toxicity, Food safety, sprague-dawley, 030104 developmental biology, oral toxicity, lcsh:Biology (General), lcsh:QD1-999, Nanoparticles, nano size, business, oral exposure, 1605 Organic Chemistry
Abstract

Titanium dioxide (TiO2) is used as a food additive (E171) and can be found in sauces, icings, and chewing gums, as well as in personal care products such as toothpaste and pharmaceutical tablets. Along with the ubiquitous presence of TiO2 and recent insights into its potentially hazardous properties, there are concerns about its application in commercially available products. Especially the nano-sized particle fraction (2 warrants a more detailed evaluation of potential adverse health effects after ingestion. A workshop organized by the Dutch Office for Risk Assessment and Research (BuRO) identified uncertainties and knowledge gaps regarding the gastrointestinal absorption of TiO2, its distribution, the potential for accumulation, and induction of adverse health effects such as inflammation, DNA damage, and tumor promotion. This review aims to identify and evaluate recent toxicological studies on food-grade TiO2 and nano-sized TiO2 in ex-vivo, in-vitro, and in-vivo experiments along the gastrointestinal route, and to postulate an Adverse Outcome Pathway (AOP) following ingestion. Additionally, this review summarizes recommendations and outcomes of the expert meeting held by the BuRO in 2018, in order to contribute to the hazard identification and risk assessment process of ingested TiO2.

Published
2021

2. How to Differentiate General Toxicity-Related Endocrine Effects from Endocrine Disruption: Systematic Review of Carbon Disulfide Data

Author

Nathalie Printemps, Brigitte Le Magueresse-Battistoni, Sakina Mhaouty-Kodja, Catherine Viguié, Cécile Michel, Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
[SDV]Life Sciences [q-bio], Organic Chemistry, thyroid disruption, cardiotoxicity, Thyroid Gland, Endocrine System, General Medicine, Endocrine Disruptors, Risk Assessment, Catalysis, Computer Science Applications, Inorganic Chemistry, Carbon Disulfide, neurotoxicity, Humans, Physical and Theoretical Chemistry, Molecular Biology, Spectroscopy
Abstract

International audience; This review provides an overview of the assessment of the endocrine disrupting (ED) properties of carbon disulfide (CS2), following the methodology used at the European level to identify endocrine disruptors. Relevant in vitro, in vivo studies and human data are analyzed. The assessment presented here focuses on one endocrine activity, i.e., thyroid disruption, and two main adverse effects, neurotoxicity and cardiotoxicity. The data available on the different ED or non-ED modes of action (MoA), known to trigger these adverse effects, are described and the strength of evidence of the different MoA is weighted. We conclude that the adverse effects could be due to systemic toxicity rather than endocrine-mediated toxicity. This assessment illustrates the scientific and regulatory challenges in differentiating a specific endocrine disruption from an indirect endocrine effect resulting from a non-ED mediated systemic toxicity. This issue of evaluating the ED properties of highly toxic and reactive substances has been insufficiently developed by European guidance so far and needs to be further addressed. Finally, this example also raises questions about the capacity of the technics available in toxicology to address such a complex issue with certainty.

Published
2022

3. Gene Expression Profiling Reveals that PXR Activation Inhibits Hepatic PPARα Activity and Decreases FGF21 Secretion in Male C57Bl6/J Mice

Author

Tiffany Fougeray, Marion Régnier, Nicolas Loiseau, Colette Bétoulières, Yannick Lippi, Arnaud Polizzi, Hervé Guillou, Laila Mselli-Lakhal, Céline Lukowicz, Frédéric Lasserre, Claire Naylies, Anne Fougerat, Sharon Barretto, Laurence Gamet-Payrastre, Sarra Smati, Sandrine Ellero-Simatos, Lorraine Smith, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Plateforme Ezop (Ezop), Exposition, Perturbation Endocrino-métabolique et Reproduction (ToxAlim-EXPER), Region Occitanie, INRA AlimH department, Agence Nationale de la Recherche (ANR), Fond Europeen de Developpement Regional (FEDER), Joint Programming Initiative (JPI), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), and ElleroSsimatos, Sandrine

Subjects
Male, FGF21, nuclear receptors, Energy homeostasis, Transcriptome, lcsh:Chemistry, transcriptomics, 0302 clinical medicine, Receptor, lcsh:QH301-705.5, Spectroscopy, 0303 health sciences, Pregnane X receptor, hepatokines, Chemistry, Pregnane X Receptor, General Medicine, 3. Good health, Computer Science Applications, Cell biology, Liver, Pregnenolone, medicine.drug, Transcriptional Activation, digestive system, Catalysis, Article, Inorganic Chemistry, 03 medical and health sciences, Autre (Chimie), medicine, Animals, PPAR alpha, Physical and Theoretical Chemistry, Molecular Biology, 030304 developmental biology, Gene Expression Profiling, Organic Chemistry, digestive system diseases, Gene expression profiling, Fibroblast Growth Factors, Mice, Inbred C57BL, Nuclear receptor, lcsh:Biology (General), lcsh:QD1-999, Other, [CHIM.OTHE]Chemical Sciences/Other, 030217 neurology & neurosurgery, Gene Deletion
Abstract

The pregnane X receptor (PXR) is the main nuclear receptor regulating the expression of xenobiotic-metabolizing enzymes and is highly expressed in the liver and intestine. Recent studies have highlighted its additional role in lipid homeostasis, however, the mechanisms of these regulations are not fully elucidated. We investigated the transcriptomic signature of PXR activation in the liver of adult wild-type vs. Pxr-/- C57Bl6/J male mice treated with the rodent specific ligand pregnenolone 16&alpha, carbonitrile (PCN). PXR activation increased liver triglyceride accumulation and significantly regulated the expression of 1215 genes, mostly xenobiotic-metabolizing enzymes. Among the down-regulated genes, we identified a strong peroxisome proliferator-activated receptor &alpha, (PPAR&alpha, ) signature. Comparison of this signature with a list of fasting-induced PPAR&alpha, target genes confirmed that PXR activation decreased the expression of more than 25 PPAR&alpha, target genes, among which was the hepatokine fibroblast growth factor 21 (Fgf21). PXR activation abolished plasmatic levels of FGF21. We provide a comprehensive signature of PXR activation in the liver and identify new PXR target genes that might be involved in the steatogenic effect of PXR. Moreover, we show that PXR activation down-regulates hepatic PPAR&alpha, activity and FGF21 circulation, which could participate in the pleiotropic role of PXR in energy homeostasis.

Published
2019

4. Adipose-Derived Stem Cells in the Treatment of Perianal Fistulas in Crohn’s Disease: Rationale, Clinical Results and Perspectives

Author

Laetitia Bugarel, Barbara Bournet, Marine Lebrin, Etienne Buscail, Louis Buscail, Fabian Gross, Céline Deraison, Guillaume Le Cosquer, Cyrielle Gilletta, Nathalie Vergnolle, Institut de Recherche en Santé Digestive (IRSD ), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), CHU Toulouse [Toulouse], Centre d'investigation clinique de Toulouse (CIC 1436), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Pôle Santé publique et médecine publique [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), and SEGUIN, Nathalie

Subjects
Crohn’s disease, Pathology, [SDV.MHEP.PHY] Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Fistula, Adipose tissue, Review, 0302 clinical medicine, Crohn Disease, allogenic stem cells, Biology (General), Spectroscopy, Clinical Trials as Topic, 0303 health sciences, Crohn's disease, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Stem Cells, General Medicine, 3. Good health, Computer Science Applications, Chemistry, Adipose Tissue, 030211 gastroenterology & hepatology, medicine.medical_specialty, Stromal cell, QH301-705.5, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Paracrine signalling, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], medicine, Animals, Humans, Rectal Fistula, Physical and Theoretical Chemistry, QD1-999, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Molecular Biology, 030304 developmental biology, mesenchymal stem cells, business.industry, Organic Chemistry, Mesenchymal stem cell, perianal fistula, medicine.disease, Clinical trial, adipose-derived stem cells, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Stem Cell Transplantation, Homing (hematopoietic)
Abstract

International audience; Between 20 to 25% of Crohn’s disease (CD) patients suffer from perianal fistulas, a marker of disease severity. Seton drainage combined with anti-TNFα can result in closure of the fistula in 70 to 75% of patients. For the remaining 25% of patients there is room for in situ injection of autologous or allogenic mesenchymal stem cells such as adipose-derived stem/stromal cells (ADSCs). ADSCs exert their effects on tissues and effector cells through paracrine phenomena, including the secretome and extracellular vesicles. They display anti-inflammatory, anti-apoptotic, pro-angiogenic, proliferative, and immunomodulatory properties, and a homing within the damaged tissue. They also have immuno-evasive properties allowing a clinical allogeneic approach. Numerous clinical trials have been conducted that demonstrate a complete cure rate of anoperineal fistulas in CD ranging from 46 to 90% of cases after in situ injection of autologous or allogenic ADSCs. A pivotal phase III-controlled trial using allogenic ADSCs (Alofisel®) demonstrated that prolonged clinical and radiological remission can be obtained in nearly 60% of cases with a good safety profile. Future studies should be conducted for a better knowledge of the local effect of ADSCs as well as for a standardization in terms of the number of injections and associated procedures.

Published
2021

5. PPARs and Microbiota in Skeletal Muscle Health and Wasting

Author

Manickam, Ravikumar, Duszka, Kalina, Wahli, Walter, University of South Florida [Tampa] (USF), University of Vienna [Vienna], ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Center for Integrative Genomics - Institute of Bioinformatics, Génopode (CIG), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL)-Université de Lausanne (UNIL), Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), and Lee Kong Chian School of Medicine (LKCMedicine)

Subjects
PPAR, gut, metabolism, microbiota, muscle, Peroxisome Proliferator-Activated Receptors, Peroxisome proliferator-activated receptor, Review, lcsh:Chemistry, 0302 clinical medicine, lcsh:QH301-705.5, Wasting, Spectroscopy, chemistry.chemical_classification, 0303 health sciences, Muscle Weakness, General Medicine, Muscle atrophy, Computer Science Applications, Muscular Atrophy, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, medicine.anatomical_structure, Muscle, medicine.symptom, Signal Transduction, medicine.medical_specialty, Inflammation, Biology, Protein degradation, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Internal medicine, medicine, Animals, Humans, Medicine [Science], Physical and Theoretical Chemistry, Muscle, Skeletal, Molecular Biology, 030304 developmental biology, Organic Chemistry, Skeletal muscle, Endocrinology, lcsh:Biology (General), lcsh:QD1-999, chemistry, Nuclear receptor, Mitochondrial biogenesis, Energy Metabolism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, 030217 neurology & neurosurgery
Abstract

Skeletal muscle is a major metabolic organ that uses mostly glucose and lipids for energy production and has the capacity to remodel itself in response to exercise and fasting. Skeletal muscle wasting occurs in many diseases and during aging. Muscle wasting is often accompanied by chronic low-grade inflammation associated to inter- and intra-muscular fat deposition. During aging, muscle wasting is advanced due to increased movement disorders, as a result of restricted physical exercise, frailty, and the pain associated with arthritis. Muscle atrophy is characterized by increased protein degradation, where the ubiquitin-proteasomal and autophagy-lysosomal pathways, atrogenes, and growth factor signaling all play an important role. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear receptor family of transcription factors, which are activated by fatty acids and their derivatives. PPARs regulate genes that are involved in development, metabolism, inflammation, and many cellular processes in different organs. PPARs are also expressed in muscle and exert pleiotropic specialized responses upon activation by their ligands. There are three PPAR isotypes, viz., PPARα, -β/δ, and -γ. The expression of PPARα is high in tissues with effective fatty acid catabolism, including skeletal muscle. PPARβ/δ is expressed more ubiquitously and is the predominant isotype in skeletal muscle. It is involved in energy metabolism, mitochondrial biogenesis, and fiber-type switching. The expression of PPARγ is high in adipocytes, but it is also implicated in lipid deposition in muscle and other organs. Collectively, all three PPAR isotypes have a major impact on muscle homeostasis either directly or indirectly. Furthermore, reciprocal interactions have been found between PPARs and the gut microbiota along the gut–muscle axis in both health and disease. Herein, we review functions of PPARs in skeletal muscle and their interaction with the gut microbiota in the context of muscle wasting. Accepted version

Published
2020

6. Comparison of Tumor- and Bone Marrow-Derived Mesenchymal Stromal/Stem Cells from Patients with High-Grade Osteosarcoma

Author

Le Nail, Louis-Romée, Brennan, Meadhbh, Rosset, Philippe, Deschaseaux, Frédéric, Piloquet, Philippe, Pichon, Olivier, Le Caignec, Cédric, Crenn, Vincent, Layrolle, Pierre, Hérault, Olivier, De Pinieux, Gonzague, Trichet, Valérie, Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université Bretagne Loire (UBL), Service de Chirurgie Orthopédique 2 [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT), Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS), Harvard University [Cambridge], STROMALab, Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Etablissement Français du Sang-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de génétique médicale [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Chirurgie Orthopédique [CHU Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CNRS GDR 3697 MicroNiT, Centre National de la Recherche Scientifique (CNRS), ERL 7001 LNOx (Leukemic Niche & redOx metabolism / Niche leucémique et métabolisme redOx) (LNOx), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported by INSERM, by Societe Française de Chirurgie Orthopedique et Traumatologique (SoFCOT), and by Cancéropole Grand Ouest (Penica project)., Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Université de Tours, Université de Tours-Université de Tours-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), maurice, sandrine, Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Centre National de la Recherche Scientifique (CNRS)-Microenvironnement des niches tumorales (CNRS GDR 3697 Micronit ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours (UT)-Université de Tours (UT), Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes] (INSERM U1238), Université de Tours-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Harvard School of Engineering and Applied Sciences (SEAS), GICC EA 7501, LNOx (Niche leucémique et métabolisme redOx) (LNOx), Centre National de la Recherche Scientifique (CNRS)-Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours-Université de Tours, Service d'Anatomie et Cytologie Pathologiques [CHRU Tours], and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-CHU Trousseau [APHP]

Subjects
Adult, Male, cancer stem cells, Adolescent, Karyotype, Bone Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Article, Immunophenotyping, lcsh:Chemistry, Young Adult, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bone Marrow, Cell Line, Tumor, osteosarcoma, Tumor Microenvironment, Humans, Neoplasm Metastasis, spheres, lcsh:QH301-705.5, Cells, Cultured, Neoplasm Staging, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, mesenchymal stem cells, Coculture Techniques, lcsh:Biology (General), lcsh:QD1-999, Neoplastic Stem Cells, Female, Neoplasm Grading, Biomarkers
Abstract

International audience; Osteosarcoma (OS) is suspected to originate from dysfunctional mesenchymal stromal/stem cells (MSC). We sought to identify OS-derived cells (OSDC) with potential cancer stem cell (CSC) properties by comparing OSDC to MSC derived from bone marrow of patients. This study included in vitro characterization with sphere forming assays, differentiation assays, cytogenetic analysis, and in vivo investigations of their tumorigenicity and tumor supportive capacities. Primary cell lines were isolated from nine high-grade OS samples. All primary cell lines demonstrated stromal cell characteristics. Compared to MSC, OSDC presented a higher ability to form sphere clones, indicating a potential CSC phenotype, and were more efficient at differentiation towards osteoblasts. None of the OSDC displayed the complex chromosome rearrangements typical of high grade OS and none of them induced tumors in immunodeficient mice. However, two OSDC demonstrated focused genomic abnormalities. Three out of seven, and six out of seven OSDC showed a supportive role on local tumor development, and on metastatic progression to the lungs, respectively, when co-injected with OS cells in nude mice. The observation of OS-associated stromal cells with rare genetic abnormalities and with the capacity to sustain tumor progression may have implications for future tumor treatments.

Published
2018

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