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Validation of an In Vitro Model to Study Human cartilage Responses to compression

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Engineering（科研） 2012年第10期4卷 61-64页

作者： Natalia de Isla céline Huselstein Didier Mainard Jean-Francois Stoltz cNRS UMR 7561 BiopoleFaculte de MédecineUniversite de LorraineVandoeuvreFrance UTcT CHU de NancyVandoeuvreFrance cOT CHU de NancyVandoeuvreFrance

The aim of this work was to develop an in vitro model to study mechanical compression effects on cartilage. A pressure-controlled compression device was used in this study. cartilage explants obtained from human knee were compressed at 1MPa/1Hz for 7 hours (30 min ON, 30 min OFF) under normoxia (5% cO2, 21% O2) or hypoxia (5% cO2, 5% O2). cell viability was analyzed while nitric oxide (NO) and glycosaminoglycans (GAG) release was assayed in culture media. Mechanical stimulation increased NO production and GAG release by human cartilage explants under normoxia and hypoxia culture. In normoxia and hypoxia conditions, mechanical stimulation alters human OA cartilage metabolism. There is also, an increase in matrix degradation after compression, as shown by levels of GAG found in culture media. This study put in evidence the importance of mechanical compression in the progression of the osteoarthritis and present and in vitro model for mechanobiological and pharmacological studies.

关键词： cartilage compression In Vitro Model Nitric Oxide GAG

Silk-based nerve guidance conduits with macroscopic holes modulate the vascularization of regenerating rat sciatic nerve

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Neural Regeneration Research 2025年第6期20卷 1789-1800页

作者： carina Hromada Patrick Heimel Markus Kerbl LászlóGál Sylvia Nürnberger Barbara Schaedl James Ferguson Nicole Swiadek Xavier Monforte Johannes c.Heinzel Antal Nógrádi Andreas H.Teuschl-Woller David Hercher Department Life Science Engineering University of Applied Sciences Technikum WienViennaAustria Austrian cluster for Tissue Regeneration ViennaAustria Ludwig Boltzmann Institute for Traumatology The Research Center in Cooperation with AUVAViennaAustria University clinic of Dentistry Medical University of ViennaViennaAustria Department of Plastic Reconstructive and Aesthetic SurgeryLandesklinikum Wiener Neustadt2700 Wiener NeustadtAustria Department of Anatomy Histology and EmbryologyAlbert Szent-Györgyi Medical SchoolUniversity of SzegedSzegedHungary Medical University of Vienna Department of Orthopedics and Trauma SurgeryDevision of Trauma SurgeryViennaAustria Department of Hand- PlasticReconstructive and Burn SurgeryBG Unfallklinik TuebingenUniversity of TuebingenTuebingenGermany

Peripheral nerve injuries induce a severe motor and sensory deficit. Since the availability of autologous nerve transplants for nerve repair is very limited, alternative treatment strategies are sought, including the use of tubular nerve guidance conduits(tNGcs). However, the use of tNGcs results in poor functional recovery and central necrosis of the regenerating tissue, which limits their application to short nerve lesion defects(typically shorter than 3 cm). Given the importance of vascularization in nerve regeneration, we hypothesized that enabling the growth of blood vessels from the surrounding tissue into the regenerating nerve within the tNGc would help eliminate necrotic processes and lead to improved regeneration. In this study, we reported the application of macroscopic holes into the tubular walls of silk-based tNGcs and compared the various features of these improved silk^(+) tNGcs with the tubes without holes(silk^(–) tNGcs) and autologous nerve transplants in an 8-mm sciatic nerve defect in rats. Using a combination of micro-computed tomography and histological analyses, we were able to prove that the use of silk^(+) tNGcs induced the growth of blood vessels from the adjacent tissue to the intraluminal neovascular formation. A significantly higher number of blood vessels in the silk^(+) group was found compared with autologous nerve transplants and silk^(–), accompanied by improved axon regeneration at the distal coaptation point compared with the silk^(–) tNGcs at 7 weeks postoperatively. In the 15-mm(critical size) sciatic nerve defect model, we again observed a distinct ingrowth of blood vessels through the tubular walls of silk^(+) tNGcs, but without improved functional recovery at 12 weeks postoperatively. Our data proves that macroporous tNGcs increase the vascular supply of regenerating nerves and facilitate improved axonal regeneration in a short-defect model but not in a critical-size defect model. This study suggests that further optimizatio

关键词： axon regeneration blood vessel functional recovery macroporous nerve lesion peripheral nerve repair sciatic nerve silk-based nerve guidance conduit vascularization

Mediator contributes to IgH locus VDJ rearrangements by promoting usage of most distal V segments

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cellular & Molecular Immunology 2020年第4期17卷 407-409页

作者： Iman Dalloul Zeinab Dalloul Sandrine Le Noir François Boyer Bernardo Reina-San-Martin Jeanne cook-moreau Michel cogné UMR cNRS 7276 INSERM U1262Universite de LimogesLimoges 87025France INSERM U1258 UMR CNRS 7104Institut de Genetique et de Biologie Moleculaire et CellulaireUniversitéde StrasbourgIllkirch 67400France

INTRODUcTION The immunoglobulin heavy(IgH)chain locus includes a large cluster of V,D and J segments spanning thousands of kilobases in mammals and its expression implies long-range 3D-regulation of various gene modifications.1 V(D)J recombination occurs during early B-cell ontogeny.2 It is regulated by multiple transcription factors and cis-regulatory elements,and most notably by the intronic 5′Eμelement located in the JH to cμintron.3 The intergenic control region 1(IGcR1)located between the VH and D gene clusters inhibits rearrangement of the most DH-proximal VH gene segments,while promoting usage of distal VH gene segments.4 Other downstream elements of the locus,flanking its 3′end might have more subtle roles:while the large 3′regulatory region(3′RR)shows strong internal synergies2 and behaves as a superenhancer in mature B *** deletion showed no influence on the VDJ repertoire and rather increased transcription of unrearranged V segments.3–5 Insulators binding cTcF farther downstream of the 3′RR were shown,however,to promote usage of distal VH segments.6 Altogether,there are strong indications that elements involved in long-distance regulation of transcription might also influence VDJ ***-frame splicing of VDJ exons is also needed for full Ig expression.7 Given the functional importance of gene architecture and long-range interactions for the IgH locus physiology,we explored the dependence of the VDJ repertoire on Med1,a known actor of long-range enhancer interactions.

关键词： B cells mediator VDJ repertoire

A 3D Human Liver Model of Nonalcoholic Steatohepatitis

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Journal of clinical and Translational Hepatology 2020年第4期8卷 359-370页

作者： Marion Duriez Agnes Jacquet Lucile Hoet Sandrine Roche Marie-Dominique Bock corinne Rocher Gilles Haussy Xavier Vigé Zsolt Bocskei Tamara Slavnic Valérie Martin Jean-claude Guillemot Michel Didier Aimo Kannt cécile Orsini Vincent Mikol Anne-céline Le Fèvre Translational Sciences Sanofi1 Avenue Pierre BrossoletteChilly-MazarinFrance IT&M STATS Groupe IT&MNeuilly-sur-SeineFrance Non clinical Biostatistics SanofiVitry sur SeineFrance Diabetes and cardiovascular Research SanofiIndustriepark HöchstFrankfurtGermany Institute of Experimental Pharmacology Medical Faculty MannheimUniversity of HeidelbergMannheimGermany

Background and Aims: To better understand nonalcoholic steatohepatitis (NASH) disease progression and to evaluate drug targets and compound activity, we undertook the devel-opment of an in vitro 3D model to mimic liver architecture and the NASH environment. Methods:We have developed an in vitro preclinical 3D NASH model by coculturing primary hu-man hepatocytes, human stellate cells, liver endothelial cells and Kupffer cells embedded in a hydrogel of rat collagen on a 96-well plate. A NASH-like environment was induced by ad-dition of medium containing free fatty acids and tumor ne-crosis factor-α. This model was then characterized by biochemical, imaging and transcriptomics analyses. Results:We succeeded in defining suitable culture conditions to main-tain the 3D coculture for up to 10 days in vitro, with the lowest level of steatosis and reproducible low level of inflammation and fibrosis. NASH disease was induced with a custom me-dium mimicking NASH features. The cell model exhibited the key NASH disease phenotypes of hepatocyte injury, steatosis, inflammation, and fibrosis. Hepatocyte injury was highlighted by a decrease of cYP3A4 expression and activity, without loss of viability up to day 10. Moreover, the model was able to stimulate a stable inflammatory and early fibrotic environ-ment, with expression and secretion of several cytokines. A global gene expression analysis confirmed the NASH induc-tion. conclusions:This is a new in vitro model of NASH dis-ease consisting of four human primary cell-types that exhibits most features of the disease. The 10-day cell viability and cost effectiveness of the model make it suitable for medium throughput drug screening and provide attractive avenues to better understand disease physiology and to identify and characterize new drug targets.

关键词： 3D liver model Human primary cells Key features of NASH

GISAID’s Role in Pandemic Response

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china cDc weekly 2021年第49期3卷 1049-1051页

作者： Shruti Khare céline Gurry Lucas Freitas Mark B Schultz Gunter Bach Amadou Diallo Nancy Akite Joses Ho Raphael Tc Lee Winston Yeo GISAID core curation Team Sebastian Maurer-Stroh GISAID Global Data Science Initiative(GISAID) MunichGermany Bioinformatics Institute Agency for Science Technology and ResearchSingapore Oswaldo cruz Foundation(FIOcRUZ) Rio de JaneiroBrazil Institut Pasteur de Dakar DakarSenegal National Institutes of Biotechnology Malaysia SelangorMalaysia Smorodintsev Research Institute of Influenza St.PetersburgRussia Genome Institute of Singapore Agency for Science Technology and ResearchSingapore china National GeneBank ShenzhenChina A*STAR Infectious Disease Labs(ID Labs) Singapore National Public Health Laboratory National Centre for Infectious DiseasesMinistry of HealthSingapore Department of Biological Sciences National University of SingaporeSingapore.

GISAID is a global data science initiative and the primary source of genomic and associated metadata of all influenza viruses,Respiratory Syncytial Virus(RSV)and severe acute respiratory syndrome coronavirus 2(SARS-coV-2),the pandemic coronavirus causing coronavirus disease 2019(cOVID-19).GISAID’s publicly accessible data sharing platform enables collaboration of over 42,000 participating researchers from 198 nations and data generators from over 3,500 institutions across the *** the first wholegenome sequences were made available by china cDc through GISAID on January 10.

关键词： acute respiratory AID

Major bleeding events in octagenarians associated with drug interactions between dabigatran and P-gp inhibitors

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Journal of Geriatric cardiology 2019年第11期16卷 806-811页

作者： Marjorie Bernier Sarah-line Lancrerot Fanny Rocher Elise K Van-Obberghen Pierre Olivier Thibaud Lavrut Nadège Parassol-Girard Milou-Daniel Drici Department of Pharmacology and Toxicology PharmacoVigilance CenterUniversity of Nice Côte d'Azur Medical CenterHôpital de Cimiez4 Avenue Reine VictoriaBP 117906003NiceFrance Emergency Department Short Stay Unit University of Nice Côte d'Azur Medical CenterHôpital Pasteur 230Voie Romaine 06001NiceFrance

Background The direct oral anticoagulant dabigatran does not require any routine therapeutic drug ***,concerns about possible drug interactions susceptible to increase its inherent bleeding risk,especially in very elderly patients,have been raised *** aim of our study was to evaluate to what extent the co-prescription of P-gp inhibitors with dabigatran may increase its plasma levels and lead to bleeding complications,in usual conditions of care of the very *** Fifty-eight patients over 85 years old with non valvular atrial fibrillation receiving dabigatran were included in a prospective *** were screened for the presence of P-gp inhibitors(Group A)or not(Group B).Results Patients from Group A had increased dabigatran mean plasma concentrations as compared with patients from Group B(A vs.B:182.2±147.3 vs.93.7±64.9 ng/m L).One third of the patients from Group A had dabigatran concentrations that were deemed"out of range"versus none in Group B(P=0.05).This was associated with more frequent bleeding complications in Group A(A:30.4%,B:8.6%,P=0.04).conclusion In our cohort of very elderly patients,at least,the co-prescription of dabigatran with P-gp inhibitors in usual conditions of care resulted in higher dabigatran plasma concentrations and more frequent bleeding occurrences.

关键词： Dabigatran Drug interaction Hemorrhage P-gp inhibitors,The elderly

Immunosuppression and Increased Risk of Bacterial Infections in cirrhosis

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Infectious Microbes & Diseases 2021年第3期3卷 115-116页

作者： Richard moreau Vicente Arroyo European Foundation for Study of chronic Liver Failure EF-CiifBarcelonaSpain Liver Unit APHPBeaujon HospitalClichyFrance Paris University INSERMCNRSCenter for Research on Inflammation(CRI)ParisFrance

Immunosuppression and Increased Risk of Bacterial Infections in cirrhosis Richard moreau1,2,3,131,Vicente Arroyo1 cirrhosis is one of the commonest causes of death among middle-aged persons worldwide.1 A universal observation is that bacterial infections,alone or combined with acute hepatitis(related to,for example,excessive alcohol consumption or a flare of hepatitis B virus infection),frequently precipitate acutely decompensated cirrhosis,leading to hospitalization of patients.

关键词： acute cirrhosis hepatitis

Fast Fatty Acid Analysis by core-Shell Reversed-Phase Liquid chromatography coupled to Evaporative Light-Scattering Detector

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Food and Nutrition Sciences 2017年第12期8卷 1051-1062页

作者： Florence Hubert céline Loiseau Francoise Ergan Gaelle Pencréac’h Laurent Poisson Laboratoire Mer MoléculesSanté(EA 2160)Le Mans UniversitéIUT de LavalLavalFrance

A high-performance liquid chromatography analysis method with an evaporative light-scattering detector has been developed for the separation and quantitative analysis of free fatty acids in biological matrices. core-shell reversed-phase high-performance liquid chromatography separation of 10 free fatty acids is achieved within 10.5 min using a methanol/water (0.05% trifluoroacetic acid) eluent gradient. After optimization, the drift tube and nebulization temperature of the evaporative light-scattering detector was set at 35°c, nitrogen flow-rate at 1.1 standard liter per minute and column temperature at 25°c. All calibration curves showed good regression (r2 > 0.9975). A validation procedure following the International conference on Harmonisation guidelines was implemented to certify the method. Relative standard deviations did not exceed 1.5% and 4.25% for repeatability and reproducibility respectively.

关键词： Free Fatty Acids HPLc Evaporative Light-Scattering Detector core-Shell Technology Method Validation

Differentiation of hMSc in Micromass culture

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生物医学工程学杂志 2005年第S1期22卷 153-154页

作者： Jing-WEI YANG Natalia De ISIA céline HUSELSTEIN Luc MARcHAL Marie-Nathalie SARDA-KOLOPP Jing-Ping OUYANG Jean-Fran·ois STOL TZ Assia ELJAAFARI Research Group of cell and Tissue Engineering LEMTA-CNRS UMR 7563Facultéde Médecine de NancyUHP and CHU NancyFrance Department of Pathophysiology Medical College of Wuhan UniversityWuhan 430071China Immunology Laboratory Faculty of MedicineUHP Nancy 1Vandoeuvre-lès-NancyFrance

1 Introduction Mesenchymal stem cells(MScs)are multipotential stem cells which can be expanded in culture while still maintaining their undifferentiated *** have the potential to differentiate into distinct mesenchymal tissue cells,including ***,they are an attrac2 tive cell source for cartilage ti ssue *** vitro high density micromass culture has been widely used for chondrogenesis *** objective of our study was to analyze viability and differentiation of hMSc in micro2 mass cultures.

关键词： stem cells tissue engineering high density