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Embedding MSCs in Si-HPMC hydrogel decreased MSC-directed host immune response and increased the regenerative potential of macrophages

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Regenerative Biomaterials 2022年第1期9卷 490-500页

作者： Christelle demarquay Lara Moussa Gildas Réethorée Fabien Milliat Pierre Weiss Noëlle Mathieu Human Health department IRSNFrench Institute for Radiological Protection and Nuclear SafetySERAMEDLRMedFontenay-aux-Roses 92262France Facultéde chirurgie dentaire Regenerative Medicine and Skeleton(RMeS)LaboratoryUniversite de NantesNantes 44042France

Embedding mesenchymal stromal cells(MSCs)in biomaterial is a subject of increasing interest in the field of Regenerative *** up the clinical use of MSCs is dependent on the use of non-syngeneic models in accordance with Good Manufacturing Practices(GMP)requirements and on *** this end,in this study,we analyzed the in vivo host immune response following local injection of silanized hydroxypropyl methylcellulose(Si-HPMC)-embedded human MSCs in a rat model developing colorectal damage induced by ionizing *** and lymphocytes from mesenteric lymph nodes were harvested in addition to colonic *** set up tests,using flow cytometry and a live imaging system,to highlight the response to specific antibodies and measure the cytotoxicity of lymphocytes against injected *** demonstrated that Si-HPMC protects MSCs from specific antibodies production and from apoptosis by *** also observed that Si-HPMC does not modify innate immune response infiltrate in vivo,and that in vitro co-culture of Si-HPMC-embedded MSCs impacts macrophage inflammatory response depending on the microenvironment but,more importantly,increases the macrophage regenerative response through Wnt-family and VEGF gene *** study furthers our understanding of the mechanisms involved,with a view to improving the therapeutic benefits of biomaterial-assisted cell therapy by modulating the host immune *** decrease in specific immune response against injected MSCs protected by Si-HPMC also opens up new possibilities for allogeneic clinical use.

关键词： Si-HPMC hydrogel mesenchymal stromal cells host immune response regenerative medicine

Temporomandibular joint damage in K/BxN arthritic mice

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International Journal of Oral Science 2020年第1期12卷 59-67页

作者： Sabine Kuchler-Bopp Alexandre Mariotte Marion Strub Chrystelle Po Aurore de Cauwer Georg Schulz Xavier Van Bellinghen Florence Fioretti Francois Clauss Philippe Georgel Nadia Benkirane-Jessel Fabien Bornert INSERM(French National Institute of Health and Medical Research) UMR 1260Regenerative NanoMedicine(RNM)FMTSStrasbourgFrance INSERM UMR 1109Immuno Rhumatologie Moléculaire(IRM)FMTSStrasbourgFrance Fédération Hospitalo-Universitaire(FHU)OMICARE Universitéde StrasbourgStrasbourgFrance Facultéde chirurgie dentaire Universitéde Strasbourg(UDS)8 rue Ste ElisabethStrasbourgFrance Pole de Médecine et chirurgie Bucco-dentaires Hopitaux Universitaires de Strasbourg(HUS)1 place de l’HopitalStrasbourgFrance ICube UMR 7357 Universitéde StrasbourgCNRSFMTS4 rue KirschlegerStrasbourgFrance department of Biomedical Engineering Core Facility Micro-and NanotomographyBiomaterials Science Center(BMC)University of BaselGewerbestrasse 144123AllschwilSwitzerland

Rheumatoid arthritis(RA) is an autoimmune disease affecting 1% of the world population and is characterized by chronic inflammation of the joints sometimes accompanied by extra-articular manifestations. K/Bx N mice, originally described in 1996 as a model of polyarthritis, exhibit knee joint alterations. The aim of this study was to describe temporomandibular joint(TMJ)inflammation and damage in these mice. We used relevant imaging modalities, such as micro-magnetic resonance imaging(μMRI)and micro-computed tomography(μCT), as well as histology and immunofluorescence techniques to detect TMJ alterations in this mouse model. Histology and immunofluorescence for Col-I, Col-II, and aggrecan showed cartilage damage in the TMJ of K/Bx N animals, which was also evidenced by μCT but was less pronounced than that seen in the knee joints. μMRI observations suggested an increased volume of the upper articular cavity, an indicator of an inflammatory process. Fibroblast-like synoviocytes(FLSs)isolated from the TMJ of K/Bx N mice secreted inflammatory cytokines(IL-6 and IL-1β) and expressed degradative mediators such as matrix metalloproteinases(MMPs). K/Bx N mice represent an attractive model for describing and investigating spontaneous damage to the TMJ, a painful disorder in humans with an etiology that is still poorly understood.

关键词： damage alterations inflammation

Characterization of two rat models of cystic fibrosis—KO and F508del CFTR—Generated by Crispr-Cas9

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Animal Models and Experimental Medicine 2019年第4期2卷 297-311页

作者： Elise dreano Marc Bacchetta Juliette Simonin Louise Galmiche Claire Usal Lotfi Slimani Jérémy Sadoine Laurent Tesson Ignacio Anegon Jean-Paul Concordet Aurélie Hatton Lucile Vignaud danielle Tondelier Isabelle Sermet-Gaudelus Marc Chanson Charles-Henry Cottart INSERM 1151 INEMUniversitéde ParisParisFrance département de Pédiatrie Gynécologie&Obstétrique et Département de Physiologie Cellulaire&MétabolismeUniversitéde GenèveGenèveSwitzerland département de Pathologie APHPCHU Necker-Enfants MaladesParisFrance Centre de Recherche en Transplantation&Immunologie UMR 1064INSERMUniversitéde NantesNantesFrance Plateforme Trangénèse Rat&ImmunoPhénomique INSERM 1064&SFR François BonamyCNRS UMS3556NantesFrance Pathologie Imagerie&Biothérapies OrofacialesMontrougeFrance Plateforme Imageries du vivant Facultéde chirurgie dentaireUniversitéde ParisParisFrance INSERM U1154 CNRS UMR7196MNHNTACGENEParisFrance AP-HP Centre Maladie Rare Mucoviscidose et Maladies du CFTRAssistance Publique Hôpitaux de ParisHôpital Necker-Enfants MaladesParisFrance Facultéde Médecine de Paris Universitéde ParisParisFrance Facultéde Pharmacie de Paris Universitéde ParisParisFrance

Background: Genetically engineered animals are essential for gaining a proper understanding of the disease mechanisms of cystic fibrosis(CF). The rat is a relevant laboratory model for CF because of its zootechnical capacity, size, and airway characteristics, including the presence of submucosal ***: We describe the generation of a CF rat model(F508 del) homozygous for the ***508 del mutation in the transmembrane conductance regulator(Cftr) gene. This model was compared to new Cftr-/-rats(CFTR KO). Target organs in CF were examined by histological staining of tissue sections and tooth enamel was quantified by micro-computed tomography. The activity of CFTR was evaluated by nasal potential difference(NPd) and short-circuit current measurements. The effect of VX-809 and VX-770 was analyzed on nasal epithelial primary cell cultures from F508 del ***: Both newborn F508 del and Knock out(KO) animals developed intestinal obstruction that could be partly compensated by special diet combined with an osmotic laxative. The two rat models exhibited CF phenotypic anomalies such as vas deferens agenesis and tooth enamel defects. Histology of the intestine, pancreas, liver, and lungs was normal. Absence of CFTR function in KO rats was confirmed ex vivo by short-circuit current measurements on colon mucosae and in vivo by NPd, whereas residual CFTR activity was observed in F508 del rats. Exposure of F508 del CFTR nasal primary cultures to a combination of VX-809 and VX-770 improved CFTR-mediated ***: The F508 del rats reproduce the phenotypes observed in CFTR KO animals and represent a novel resource to advance the development of CF therapeutics.

关键词： animal models CFTR channel activity CFTR modulators cystic fibrosis primary cultures rat

Polydopamine Particles Effect on Melanoma Cells Proliferation and Melanin Secretion

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Advances in Chemical Engineering and Science 2013年第3期3卷 1-10页

作者： Sandy Eap Alice Ferrand Valérie Machi Vincent Ball Olivier Huck Nadia Benkirane-Jessel INSERM Institut National de la Santé et de la Recherche Médicale “Osteoarticular and Dental Regenerative Nanomedicine” Team Strasbourg France Université de Strasbourg Faculté de Chirurgie Dentaire Strasbourg France

Melanin is a biopolymer implicated in the protection of cellular membranes and dNA produced by melanocytes. This pigment has a dual role and should be considered as a photo-protector and as a photosensitizer due to its interaction with UV. The design of multifunctional and biologically responsive coatings is of major interest in modern biomaterials science. The aim of this study is not only to characterize the deposition of multilayered polyelectrolytes films made from polydopamine particles and polyamines like poly-(L-lysine hydrobromide) (PLL), but also to evaluate melanoma cells activity in terms of proliferation and their capacity to stimulate melanin secretion. One could expect that the presence of a melanin like material in the film may have a positive or a negative feedback on the melanin biosynthesis and consequently on melanoma development. Some comparisons are also done with pure polydopamine grains in suspension in the cell culture medium, to investigate if the immobilization of the polydopamine grains has an influence on their bioactivity.

关键词： Polydopamine Particles Polyelectrolyte Multilayers Films Melanin Melanoma Cells

Unbinding Process of Amelogenin and Fibrinogen Adsorbed on different Solid Surfaces Using AFM

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Journal of Biomaterials and Nanobiotechnology 2011年第3期2卷 244-249页

作者： Ludovic Richert Abdessamad Boukari Simon Berner Michel dard Joseph Hemmerlé Institut National de la Sante et de la Recherche Medicale Faculte de chirurgie dentaire Universite de Strasbourg Centre National de la Recherche Scientifique Faculte de pharmacie Universite de Strasbourg Institut Straumann AG

The interaction of proteins with solid surfaces is a fundamental phenomenon in the biomaterials field. We investigated, using atomic force microscopy (AFM), the interactions of a recombinant amelogenin with titanium, a biphasic calcium phosphate (BCP) and mica. The unbinding processes were compared to those of an earlier studied protein, namely fibrinogen. Force spectroscopy (AFM) experiments were carried out at 0 ms, 102 ms, 103 ms and 104 ms of contact time. In general, the rupture forces increased as a function of interaction time. The unbinding forces of amelogenin interacting with the BCP surface were always stronger than those of the amelogenin-titanium system. The unbinding forces of fibrinogen interacting with the BCP surface were always much stronger than those of the fibrinogen-titanium system. For the most part, this study provides direct evidence that recombinant amelogenin binds more strongly than fibrinogen on the studied substrates.

关键词： Amelogenin Titanium Calcium phosphate Force-mode AFM

Nanostructured hybrid materials for bone-tooth unit regeneration

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Open Journal of Regenerative Medicine 2013年第3期2卷 47-52页

作者： Sabine Kuchler-Bopp Thibault Becavin Tunay Kokten Florence Fioretti etienne deveaux Nadia Benkirane-Jessel Laetitia Keller Institut National de la Santeet de la Recherche Medicale(INSERM) UMR 1109Osteoarticular and Dental RegenerativeNanomedicineFacultede MedecineStrasbourgFrance Universitede Strasbourg Facultede Chirurgie Dentaire1 Place de l’HopitalStrasbourgFrance 3.UniversitéLille Nord de FranceFacultede Chirurgie DentaireLilleFrance

As a part of regenerative medicine, biomaterials are largely used in this field of nanotechnology and tissue engineering research. We have recently developed a new scaffold using electrospun nanofibers of Poly (ε-caprolactone), PCL which is able to mimic the collagen extracellular matrix of cells. The aim of this study was to engineer a biological and implantable structure leading the regeneration of the tooth-bone unit. For this aim, we have cultured mouse osteoblasts embedded in a collagen gel on the nanofibrous membrane and coupled this structure with an embryonic dental germ before implantation. To follow bone and tooth regeneration, we have performed RT-PCR, histology and immunofluorescence analysis. We showed here that this leaving implantable structure represents an accurate strategy for bone-tooth unit regeneration. We report here the first demonstration of bone-tooth unit regeneration by using a strategy based on a synthetic nanostructured membrane. This electrospun membrane is manufactured by using an FdA approved polymer, PCL and functionalized with osteoblasts before incorporation of the tooth germs at Ed14 (the first lower molars) to generate bone-tooth unit in vivo after implantation in mice. Our technology represents an excellent platform on which other sophisticated products could be based.

关键词： Bone Nanostructured Material Osteoblast Tissue Engineering Tooth

跨膜蛋白Syndecan-1在不同发育时期小鼠磨牙组织中的表达

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华西口腔医学杂志 2008年第3期26卷 316-319页

作者：高洁 Lesot H 中国医科大学口腔医院儿童牙科辽宁沈阳110002 Faculte de chirurgie dentaire Universite Louis PasteurStrasbourgFrance

目的以小鼠磨牙为发育模型,研究其不同发育时期跨膜蛋白Syndecan-1的表达特点,进而分析Syndecan-1在牙齿发育中的作用。方法取不同胎龄的胎鼠,制作其下颌第一磨牙的切片,进行免疫荧光染色,并在荧光显微镜下观察Syndecan-1的表达情况。结... 详细信息

目的以小鼠磨牙为发育模型,研究其不同发育时期跨膜蛋白Syndecan-1的表达特点,进而分析Syndecan-1在牙齿发育中的作用。方法取不同胎龄的胎鼠,制作其下颌第一磨牙的切片,进行免疫荧光染色,并在荧光显微镜下观察Syndecan-1的表达情况。结果Syndecan-1的表达随牙胚发育的时期不同而变化:蕾状期时在牙源性上皮和间充质中有弱的阳性分布,帽状期时成釉器上皮阳性表达减弱,而牙乳头及周围的间充质的阳性反应明显增强,钟状期时成釉器上皮又呈阳性表达,并以在中间细胞层的反应更为强烈,而牙乳头间充质的染色则很弱,同时前成釉细胞以及下方的成牙本质细胞的顶端也呈Syndecan-1的阳性表达。结论Syndecan-1参与了成釉器和牙乳头的发育和分化过程的调节,并与牙胚细胞的增殖以及成釉细胞和成牙本质细胞的分化相关。

关键词：跨膜蛋白Syndecan-1 牙胚牙发育

Isolation and Identification of Two Antibacterial Agents from <i>Chromolaena odorata</i>L. Active against Four diarrheal Strains

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Advances in Microbiology 2013年第1期3卷 115-121页

作者： Ménonvè Atindehou Latifou Lagnika Bernard Guérold Jean Marc Strub Minjie Zhao Alain Van dorsselaer Eric Marchioni Gilles Prévost Youssef Haikel Corinne Taddéi Ambaliou Sanni Marie-Hélène Metz-Boutigue CNRS UMR7178 University of Strasbourg Strasbourg France EA 7290 University of Strasbourg Strasbourg France Faculté de chirurgie dentaire Université de Strasbourg Strasbourg France Inserm UMR 1121 University of Strasbourg Strasbourg France IPHC-dSA CNRS University of Strasbourg Strasbourg France Université d’Abomey-Calavi Laboratoire de Biochimie et Biologie Moléculaire (LBBM) Cotonou Bénin

Chromolaena odorata L (Asteraceae) is a bad invasive plant, found in the humid tropics and sub-tropics worldwide. It is used against dysentery, diarrhea, malaria, wound healing, headache and toothache in traditional medicine. In the present study, we investigated the antibacterial activities of different leaves extracts of Chromolaena odorata L. (cyclohexane, dichloromethane, ethyl acetate and butanol) against four clinical diarrheal strains (Klebsiella oxytoca, Salmonella enterica, Shigella sonnei and Vibrio cholera). We demonstrated that C. odorata leaves extracts show an antibacterial activity between 0.156 and 1.25 mg/mL. Bioassay-guided chromatography by bioautography with iodonitrotetrazolium-based colorimetric assay allowed the isolation and identification of two active compounds. After the combination of RP-HPLC, mass spectrometry analysis, 1d and 2d-NMR spectroscopy, we isolated and characterized two active molecules corresponding to 3’,4’,5,6,7-Pentamethoxyflavone (Sinensetin) and4’,5,6,7-Tetramethoxyflavone (Scutellareintetramethyl ether).

关键词： Chromolaena odorata 3’ 4’ 5 6 7-Pentamethoxyflavone (Sinensetin) 7-Tetramethoxyflavone (Scutellareintetramethyl ether) Antibacterial Activity diarrheal Strains

Nanoscale Stiffness distribution in Bone Metastasis

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World Journal of Nano Science and Engineering 2015年第4期5卷 219-228页

作者： Ludovic Richert Laetitia Keller Quentin Wagner Fabien Bornert Catherine Gros Sophie Bahi Francois Clauss William Bacon Philippe Clézardin Nadia Benkirane-Jessel Florence Fioretti Centre National de la Recherche Scientifique(CNRS) UMRFacultéde Pharmacie de l’Universitéde Strasbourg(UdS)IllkirchFrance Institut National de la Santéet de la Recherche Médicale(INSERM) Osteoarticular and Dental Regenerative NanomedicineUMRFacultéde Médecine de l’Universitéde Strasbourg and FMTSStrasbourgFrance Facultéde chirurgie dentaire de l’Universitéde Strasbourg(UdS) StrasbourgFrance Hopitaux Universitaires de Strasbourg StrasbourgFrance Institut National de la Santéet de la Recherche Médicale(INSERM) UMRFacultéde Médecine Laennec de l’UniversitéClaude Bernard Lyon 1LyonFrance

Nanomechanical heterogeneity is expected to have an effect on elasticity, injury and bone remodelling. In normal bone, we have two types of cells (osteoclasts and osteoblasts) working together to maintain existing bone. Bone cancers can produce factors that make the osteoclasts work harder. This means that more bone is destroyed than rebuilt, and leads to weakening of the affected bone. We report here the first demonstration of the nanoscale stiffness distribution in bone metastases before and after treatment of animals with the bisphosphonate Risedronate, a drug which is currently used for the treatment of bone metastases in patients with advanced cancers. The strategy used here is applicable to a wide class of biological tissues and may serve as a new reflection for biologically inspired scaffolds technologies.

关键词： Bone Metastasis Stiffness Risedronate