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1. Surface tension of model tissues during malignant transformation and epithelial–mesenchymal transition

Author

Irène Nagle, Alain Richert, Michael Quinteros, Sébastien Janel, Edgar Buysschaert, Nathalie Luciani, Henry Debost, Véronique Thevenet, Claire Wilhelm, Céline Prunier, Frank Lafont, Teresita Padilla-Benavides, Mathieu Boissan, Myriam Reffay, Matière et Systèmes Complexes (MSC), Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Wesleyan University, Cellular Microbiology and Physics of Infection Group [Lille] (CMPI), Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Collège de France (CdF (institution))-Centre National de la Recherche Scientifique (CNRS), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Centre de Recherche Saint-Antoine (CRSA), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Plateformes Lilloises en Biologie et Santé - UAR 2014 - US 41 (PLBS), CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This work was supported by the Research Program Emergence(s) de la ville de Paris (Grant MAGIC Project), the French Defense Procurement Agency (DGA-AID), France, and Wesleyan University institutional funds., ANR-11-LABX-0071,WHO AM I,Determinants de l'Identité : de la molécule à l'individu(2011), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de biochimie et hormonologie [CHU Tenon], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Tenon [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)

Subjects
[PHYS]Physics [physics], [SDV]Life Sciences [q-bio], Cell Biology, Developmental Biology
Abstract

International audience; Epithelial–mesenchymal transition is associated with migration, invasion, and metastasis. The translation at the tissue scale of these changes has not yet been enlightened while being essential in the understanding of tumor progression. Thus, biophysical tools dedicated to measurements on model tumor systems are needed to reveal the impact of epithelial–mesenchymal transition at the collective cell scale. Herein, using an original biophysical approach based on magnetic nanoparticle insertion inside cells, we formed and flattened multicellular aggregates to explore the consequences of the loss of the metastasis suppressor NME1 on the mechanical properties at the tissue scale. Multicellular spheroids behave as viscoelastic fluids, and their equilibrium shape is driven by surface tension as measured by their deformation upon magnetic field application. In a model of breast tumor cells genetically modified for NME1, we correlated tumor invasion, migration, and adhesion modifications with shape maintenance properties by measuring surface tension and exploring both invasive and migratory potential as well as adhesion characteristics.

Published
2022

2. Development of extracellular vesicle-based medicinal products: A position paper of the group 'Extracellular Vesicle translatiOn to clinicaL perspectiVEs – EVOLVE France'

Author

Emilie Velot, Marina Trouillas, Joël Chopineau, J. Peltzer, Sophie Brouard, Olivier Favre-Bulle, Jérôme Larghero, Tristan Montier, Amanda K. A. Silva, Florence Gazeau, Phlippe Mauduit, Jean-Hugues Trouvin, Arnaud Bianchi, Noëlle Mathieu, Christian Jorgensen, Matti Ullah, Kelly Aubertin, Philippe Menasché, Surendar Arumugam, Jolanda Spadavecchia, C. Aussel, Danièle Noël, Wilfrid Boireau, M. Dedier, Sébastien Jauliac, Sébastien Banzet, Jean-Marie Bach, Antoine Monsel, Max Piffoux, Kondareddy Cherukula, Marie Morille, Célia Ravel, Christophe Martinaud, Chantal M. Boulanger, Claire Wilhelm, Mathilde Mosser, Olivier Blanc-Brude, Nicolas Sailliet, Pierre-Emmanuel Rautou, Nathalie Luciani, Isabelle Raymond-Letron, Céline Elie-Caille, Gabriel Rahmi, Anna C. Sebbagh, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC), Interactions cellules souches-niches : physiologie, tumeurs et réparation tissulaire, Service de Santé des Armées-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Ingénierie Moléculaire et Physiopathologie Articulaire (IMoPA), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC (UMR_S 970/ U970)), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), CHU Pontchaillou [Rennes], Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Franche-Comté Électronique Mécanique, Thermique et Optique - Sciences et Technologies (UMR 6174) (FEMTO-ST), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), 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), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Immuno-Endocrinologie Cellulaire et Moléculaire, Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire, Agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Chimie, Structures et Propriétés de Biomatériaux et d'Agents Thérapeutiques (CSPBAT), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Sorbonne Paris Nord, Centre de Recherche en Transplantation et Immunologie (U1064 Inserm - CRTI), 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), Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Centre de recherche sur l'Inflammation (CRI (UMR_S_1149 / ERL_8252 / U1149)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), Université de Paris (UP), Immunologie - Immunopathologie - Immunothérapie [CHU Pitié Salpêtrière] (I3), CHU Charles Foix [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors., Morille, Marie, Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Technologie de Belfort-Montbeliard (UTBM)-Ecole Nationale Supérieure de Mécanique et des Microtechniques (ENSMM)-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), 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), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Institut National de la Recherche Agronomique (INRA)-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Laboratoire de Radiobiologie des expositions médicales (IRSN/PSE-SANTE/SERAMED/LRMed), Service de recherche en radiobiologie et en médecine régénérative (IRSN/PSE-SANTE/SERAMED), Institut de Radioprotection et de Sûreté Nucléaire (IRSN)-Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), Laboratoire MSC Matière et Systèmes Complexes, Université de Paris, CNRS UMR 7057, 75006 Paris, France., Matière et Systèmes Complexes (MSC), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement Français du Sang-Centre National de la Recherche Scientifique (CNRS), Université de Paris - UFR Médecine [Santé] (UP Médecine), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Université de Montpellier (UM), Centre Léon Bérard [Lyon], Hôpital Paul Brousse, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CIC - Biotherapie - Saint Louis ((CIC-BT 301)), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Laboratoire d'HistoPathologie Expérimentale et Comparée [Toulouse] (LabHPEC), SCIENCES BIOLOGIQUES ET FONCTIONNELLES, Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre de Transfusion Sanguine des Armées (CTSA), Service de Santé des Armées, Immuno-Endocrinologie Cellulaire et Moléculaire (IECM), Université de Nantes (UN)-Ecole Nationale Vétérinaire de Nantes-École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École nationale vétérinaire, agroalimentaire et de l'alimentation Nantes-Atlantique (ONIRIS), Institut de Recherche Biomédicale des Armées (IRBA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre de Recherche en Transplantation et Immunologie - Center for Research in Transplantation and Translational Immunology (U1064 Inserm - CR2TI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Nantes Université - UFR de Médecine et des Techniques Médicales (Nantes Univ - UFR MEDECINE), Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ)-Nantes Université - pôle Santé, Nantes Université (Nantes Univ)-Nantes Université (Nantes Univ), Institut de transplantation urologie-néphrologie (ITUN), Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Hôpital Beaujon [AP-HP], Centre de référence des Maladies Vasculaires du Foie [Paris] (FILFOIE), Institut de Recherche Saint-Louis - Hématologie Immunologie Oncologie (Département de recherche de l’UFR de médecine, ex- Institut Universitaire Hématologie-IUH) (IRSL), and CHU Pitié-Salpêtrière [AP-HP]

Subjects
Quality Control, Knowledge management, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Biological medicinal products, media_common.quotation_subject, Drug Compounding, [SDV]Life Sciences [q-bio], Regulatory requirements, Pharmaceutical Science, Marketing authorization, Exosomes, Chemistry Techniques, Analytical, 03 medical and health sciences, Extracellular Vesicles, 0302 clinical medicine, Drug Development, Drug Stability, [CHIM]Chemical Sciences, Humans, Quality (business), ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, media_common, Cell-free therapy, Secretome, 0303 health sciences, Clinical Trials as Topic, Clinical-grade EV, Scientific progress, business.industry, Drug Administration Routes, Extracellular vesicle, Drugs, Investigational, Regulatory affairs, 3. Good health, [SDV.BIO] Life Sciences [q-bio]/Biotechnology, Clinical trial, Europe, Analytics, 030220 oncology & carcinogenesis, Position paper, Medicinal products, Business, Microvesicles
Abstract

International audience; Extracellular vesicles (EV) are emergent therapeutic effectors that have reached clinical trial investigation. To translate EV-based therapeutic to clinic, the challenge is to demonstrate quality, safety, and efficacy, as required for any medicinal product. EV research translation into medicinal products is an exciting and challenging perspective. Recent papers, provide important guidance on regulatory aspects of pharmaceutical development, defining EVs for therapeutic applications and critical considerations for the development of potency tests. In addition, the ISEV Task Force on Regulatory Affairs and Clinical Use of EV-based Therapeutics as well as the Exosomes Committee from the ISCT are expected to contribute in an active way to the development of EV-based medicinal products by providing update on the scientific progress in EVs field, information to patients and expert resource network for regulatory bodies. The contribution of our work group "Extracellular Vesicle translatiOn to clinicaL perspectiVEs - EVOLVE France", created in 2020, can be positioned in complement to all these important initiatives. Based on complementary scientific, technical, and medical expertise, we provide EV-specific recommendations for manufacturing, quality control, analytics, non-clinical development, and clinical trials, according to current European legislation. We especially focus on early phase clinical trials concerning immediate needs in the field. The main contents of the investigational medicinal product dossier, marketing authorization applications, and critical guideline information are outlined for the transition from research to clinical development and ultimate market authorization.

Published
2021

3. Magnetic nanoparticles in regenerative medicine: what of their fate and impact in stem cells?

Author

A. Van de Walle, Jose E. Perez, Claire Wilhelm, Nathalie Luciani, Miryana Hémadi, Ali Abou-Hassan, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP), PHysicochimie des Electrolytes et Nanosystèmes InterfaciauX (PHENIX), Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Interfaces, Traitements, Organisation et Dynamique des Systèmes (ITODYS (UMR_7086)), and Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP)

Subjects
magnetic nanoparticles, iron oxide, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Cellular differentiation, Cell, Nanotechnology, 02 engineering and technology, [CHIM.INOR]Chemical Sciences/Inorganic chemistry, 010402 general chemistry, 01 natural sciences, Regenerative medicine, biodegradation, Biomaterials, stem cells, Materials Chemistry, medicine, iron metabolism, Chemistry, 021001 nanoscience & nanotechnology, Condensed Matter Physics, nanomedicine, 0104 chemical sciences, 3. Good health, Electronic, Optical and Magnetic Materials, Cell system, Cell metabolism, medicine.anatomical_structure, Magnetic nanoparticles, Cell response, [SDV.IB]Life Sciences [q-bio]/Bioengineering, Stem cell, 0210 nano-technology
Abstract

International audience; With advancing developments over the use of magnetic nanoparticles in biomedical engineering, and more specifically cell-based therapies, the question of their fate and impact once internalized within (stem) cells remains crucial. After highlighting the regenerative medicine applications based on magnetic nanoparticles, this review documents their potential cytotoxicity and, more importantly, underscores their valuable features for stem cell differentiation. It then focuses on the transformations magnetic nanoparticles might experience in cells, mainly consisting in their progressive degradation, and assesses the practical pitfalls related to this degradation. First, it may result in a loss of long-term theranostic potential, and second, it necessitates an adaptation of the cell metabolism to the released iron. Overall, this review demonstrates that magnetic nanoparticles present undeniable interest for stem cell-based biomedical applications; however, each nanoparticle/cell system must be carefully considered for a safe medical use. It also clearly evidences that the biodegradation of the nanoparticles and the cell response to the released iron must be systematically assessed.

Published
2020

4. A 3D magnetic tissue stretcher for remote mechanical control of embryonic stem cell differentiation

Author

Vicard, Du, Nathalie, Luciani, Sophie, Richard, Gaëtan, Mary, Cyprien, Gay, François, Mazuel, Myriam, Reffay, Philippe, Menasché, Onnik, Agbulut, Claire, Wilhelm, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches et Biothérapies (CSB), Adaptation Biologique et Vieillissement = Biological Adaptation and Ageing (B2A), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), ANR-11-JSV5-0006,MagStem,Contraindre et organiser des cellules souches : rôle dans la différenciation et implication pour l'ingénierie tissulaire.(2011), ANR-10-LABX-0073,REVIVE,Stem Cells in Regenerative Biology and Medicine(2010), European Project: 648779,H2020,ERC-2014-CoG,MaTissE(2015), HAL UPMC, Gestionnaire, Jeunes Chercheuses et Jeunes Chercheurs - Contraindre et organiser des cellules souches : rôle dans la différenciation et implication pour l'ingénierie tissulaire. - - MagStem2011 - ANR-11-JSV5-0006 - JCJC - VALID, Laboratoires d'excellence - Stem Cells in Regenerative Biology and Medicine - - REVIVE2010 - ANR-10-LABX-0073 - LABX - VALID, Magnetic approaches for Tissue Mechanics and Engineering - MaTissE - - H20202015-07-01 - 2020-06-30 - 648779 - VALID, Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Dpt Cardiologie [CHU Georges Pompidou], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), and Matière et Systèmes Complexes (MSC)

Subjects
Male, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cell Survival, Science, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Cell Culture Techniques, Cell Differentiation, Mice, Inbred Strains, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, equipment and supplies, Ferric Compounds, Article, Magnetics, embryonic structures, Animals, lcsh:Q, biological phenomena, cell phenomena, and immunity, Magnetite Nanoparticles, lcsh:Science, human activities, [SDV.BC] Life Sciences [q-bio]/Cellular Biology, Embryoid Bodies, Embryonic Stem Cells, reproductive and urinary physiology
Abstract

The ability to create a 3D tissue structure from individual cells and then to stimulate it at will is a major goal for both the biophysics and regenerative medicine communities. Here we show an integrated set of magnetic techniques that meet this challenge using embryonic stem cells (ESCs). We assessed the impact of magnetic nanoparticles internalization on ESCs viability, proliferation, pluripotency and differentiation profiles. We developed magnetic attractors capable of aggregating the cells remotely into a 3D embryoid body. This magnetic approach to embryoid body formation has no discernible impact on ESC differentiation pathways, as compared to the hanging drop method. It is also the base of the final magnetic device, composed of opposing magnetic attractors in order to form embryoid bodies in situ, then stretch them, and mechanically stimulate them at will. These stretched and cyclic purely mechanical stimulations were sufficient to drive ESCs differentiation towards the mesodermal cardiac pathway., The development of embryoid bodies that are responsive to external stimuli is of great interest in tissue engineering. Here, the authors culture embryonic stem cells with magnetic nanoparticles and show that the presence of magnetic fields could affect their aggregation and differentiation.

Published
2017

5. 3D magnetic stem cell aggregation and bioreactor maturation for cartilage regeneration

Author

Nathalie Luciani, Aurore Van de Walle, Claire Wilhelm, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), ANR-11-JSV5-0006,MagStem,Contraindre et organiser des cellules souches : rôle dans la différenciation et implication pour l'ingénierie tissulaire.(2011), European Project: 648779,H2020,ERC-2014-CoG,MaTissE(2015), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), and Matière et Systèmes Complexes (MSC)

Subjects
0301 basic medicine, [SDV.BIO]Life Sciences [q-bio]/Biotechnology, Cellular differentiation, General Chemical Engineering, cartilage defect, Bioreactor, Gene Expression, Bioengineering, 02 engineering and technology, Cartilage metabolism, General Biochemistry, Genetics and Molecular Biology, Extracellular matrix, 03 medical and health sciences, Magnetics, Bioreactors, Chondrocytes, Tissue engineering, Polysaccharides, chondrogenesis, Humans, Regeneration, Collagen Type II, Aggrecan, Cell Aggregation, General Immunology and Microbiology, Tissue Scaffolds, Chemistry, General Neuroscience, Cell Differentiation, Mesenchymal Stem Cells, Anatomy, Magnetic mesenchymal stem cells, 021001 nanoscience & nanotechnology, Chondrogenesis, equipment and supplies, Cell aggregation, Cell biology, Extracellular Matrix, Magnetic forces, 030104 developmental biology, Cartilage, Magnetic Fields, Stem cell, 0210 nano-technology
Abstract

International audience; Cartilage engineering remains a challenge due to the difficulties in creating an in vitro functional implant similar to the native tissue. An approach recently explored for the development of autologous replacements involves the differentiation of stem cells into chondrocytes. To initiate this chondrogenesis, a degree of compaction of the stem cells is required; hence, we demonstrated the feasibility of magnetically condensing cells, both within thick scaffolds and scaffold-free, using miniaturized magnetic field sources as cell attractors. This magnetic approach was also used to guide aggregate fusion and to build scaffold-free, organized, three-dimensional (3D) tissues several millimeters in size. In addition to having an enhanced size, the tissue formed by magnetic-driven fusion presented a significant increase in the expression of collagen II, and a similar trend was observed for aggrecan expression. As the native cartilage was subjected to forces that influenced its 3D structure, dynamic maturation was also performed. A bioreactor that provides mechanical stimuli was used to culture the magnetically seeded scaffolds over a 21-day period. Bioreactor maturation largely improved chondrogenesis into the cellularized scaffolds; the extracellular matrix obtained under these conditions was rich in collagen II and aggrecan. This work outlines the innovative potential of magnetic condensation of labeled stem cells and dynamic maturation in a bioreactor for improved chondrogenic differentiation, both scaffold-free and within polysaccharide scaffolds.

Published
2017

6. Combining magnetic nanoparticles with cell derived microvesicles for drug loading and targeting

Author

Amanda K. A. Silva, Kelly Aubertin, Claire Wilhelm, Florence Gazeau, Stéphanie Bonneau, Nathalie Luciani, Cédric Chauvierre, Didier Letourneur, Bonneau, Stéphanie, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Jean Perrin (LJP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Biologie Paris Seine (IBPS), Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-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)-Université Paris Diderot - Paris 7 (UPD7), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-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)-Centre National de la Recherche Scientifique (CNRS), and Matière et Systèmes Complexes (MSC)

Subjects
Materials science, [PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Bioengineering, Nanotechnology, 02 engineering and technology, 03 medical and health sciences, chemistry.chemical_compound, Drug Delivery Systems, Cell-Derived Microparticles, Cell Line, Tumor, Neoplasms, Humans, General Materials Science, Magnetite Nanoparticles, 030304 developmental biology, 0303 health sciences, Antibiotics, Antineoplastic, [PHYS.PHYS.PHYS-BIO-PH] Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph], Vesicle, Hybrid vector, 021001 nanoscience & nanotechnology, equipment and supplies, Microvesicles, 3. Good health, Targeted drug delivery, chemistry, Doxorubicin, Drug delivery, Biophysics, Magnetofection, Molecular Medicine, Magnetic nanoparticles, Drug Screening Assays, Antitumor, 0210 nano-technology, human activities, Iron oxide nanoparticles
Abstract

Inspired by microvesicle-mediated intercellular communication, we propose a hybrid vector for magnetic drug delivery. It consists of macrophage-derived microvesicles engineered to enclose different therapeutic agents together with iron oxide nanoparticles. Here, we investigated in vitro how magnetic nanoparticles may influence the vector effectiveness in terms of drug uptake and targeting. Human macrophages were loaded with iron oxide nanoparticles and different therapeutic agents: a chemotherapeutic agent (doxorubicin), tissue-plasminogen activator (t-PA) and two photosensitizers (disulfonated tetraphenyl chlorin-TPCS2a and 5,10,15,20-tetra(m-hydroxyphenyl)chlorin-mTHPC). The hybrid cell microvesicles were magnetically responsive, readily manipulated by magnetic forces and MRI-detectable. Using photosensitizer-loaded vesicles, we showed that the uptake of microvesicles by cancer cells could be kinetically modulated and spatially controlled under magnetic field and that cancer cell death was enhanced by the magnetic targeting. From the clinical editor: In this article, the authors devised a biogenic method using macrophages to produce microvesicles containing both iron oxide and chemotherapeutic agents. They showed that the microvesicles could be manipulated by magnetic force for targeting and subsequent delivery of the drug payload against cancer cells. This smart method could provide a novel way for future fight against cancer.

Published
2015

7. The one year fate of iron oxide coated gold nanoparticles in mice

Author

Jelena Kolosnjaj-Tabi, Benoit Caron, Jeanne Volatron, Lenaic Lartigue, Florence Gazeau, Dan Elgrabli, Iris Marangon, Nathalie Luciani, Damien Alloyeau, Albert Figuerola, Yasir Javed, Teresa Pellegrino, Giammarino Pugliese, Paris-Centre de Recherche Cardiovasculaire (PARCC - UMR-S U970), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Matériaux et Phénomènes Quantiques (MPQ (UMR_7162)), Istituto Italiano di Tecnologia (IIT), Institut des Sciences de la Terre de Paris (iSTeP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Descartes - Paris 5 (UPD5)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC), Dipartimento di Scienze della Terra [Pisa], University of Pisa - Università di Pisa, Département des sciences de la Terre, Université Paris-Sud - Paris 11 (UP11), Paris-Centre de Recherche Cardiovasculaire ( PARCC - U970 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Matériaux et Phénomènes Quantiques ( MPQ ), Istituto Italiano di Tecnologia ( IIT ), Institut des Sciences de la Terre de Paris ( iSTeP ), and Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Centre National de la Recherche Scientifique ( CNRS )

Subjects
Aging, Materials science, Polymers, Surface Properties, [SDV]Life Sciences [q-bio], Static Electricity, Iron oxide, General Physics and Astronomy, Nanoparticle, [SDU.STU]Sciences of the Universe [physics]/Earth Sciences, Nanotechnology, 02 engineering and technology, Alkenes, 010402 general chemistry, Ferric Compounds, 01 natural sciences, Polyethylene Glycols, Mice, chemistry.chemical_compound, Coated Materials, Biocompatible, Animals, General Materials Science, Magnetite Nanoparticles, ComputingMilieux_MISCELLANEOUS, Maleic Anhydrides, Drug Carriers, Nanopartícules, General Engineering, Proteins, [ SDU.STU ] Sciences of the Universe [physics]/Earth Sciences, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Mice, Inbred C57BL, Nanomedicine, Liver, Nanocrystal, chemistry, Colloidal gold, Nanotoxicology, Injections, Intravenous, Nanoparticles, Surface modification, Gold, 0210 nano-technology, Proteïnes, Spleen, Iron oxide nanoparticles
Abstract

International audience; Safe implementation of nanotechnology and nanomedicine requires an in-depth understanding of the life cycle of nanoparticles in the body. Here, we investigate the long-term fate of gold/iron oxide heterostructures after intravenous injection in mice. We show these heterostructures degrade in vivo and that the magnetic and optical properties change during the degradation process. These particles eventually eliminate from the body. The comparison of two different coating shells for heterostructures, amphiphilic polymer or polyethylene glycol, reveals the long lasting impact of initial surface properties on the nanocrystal degradability and on the kinetics of elimination of magnetic iron and gold from liver and spleen. Modulation of nanoparticles reactivity to the biological environment by the choice of materials and surface functionalization may provide new directions in the design of multifunctional nanomedicines with predictable fate.

Published
2015

8. High-Resolution Cellular MRI: Gadolinium and Iron Oxide Nanoparticles for in-Depth Dual-Cell Imaging of Engineered Tissue Constructs

Author

Nathalie Luciani, Pierre Levitz, Riccardo Di Corato, Catherine Le Visage, Didier Letourneur, Claire Wilhelm, François Lux, Florence Gazeau, Olivier Tillement, Delphine Fayol, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Hémostase, bio-ingénierie et remodelage cardiovasculaires (LBPC), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut Galilée-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de physique de la matière condensée (LPMC), École polytechnique (X)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physico-Chimie des Matériaux Luminescents (LPCML), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Matière et Systèmes Complexes ( MSC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Hémostase, bio-ingénierie et remodelage cardiovasculaires ( LBPC ), Université Paris Diderot - Paris 7 ( UPD7 ) -Université Paris 13 ( UP13 ) -Université Sorbonne Paris Cité ( USPC ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Institut Galilée, Laboratoire de physique de la matière condensée ( LPMC ), École polytechnique ( X ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physico-Chimie des Matériaux Luminescents ( LPCML ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique ( CNRS ), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Galilée, Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, and Institut Lumière Matière [Villeurbanne] (ILM)

Subjects
Cell type, Materials science, Gadolinium, General Physics and Astronomy, chemistry.chemical_element, Contrast Media, Nanotechnology, 02 engineering and technology, Regenerative medicine, Sensitivity and Specificity, 030218 nuclear medicine & medical imaging, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Imaging, Three-Dimensional, Tissue engineering, medicine, Nanobiotechnology, Humans, General Materials Science, Magnetite Nanoparticles, Cells, Cultured, [PHYS]Physics [physics], medicine.diagnostic_test, Tissue Engineering, General Engineering, Endothelial Cells, Reproducibility of Results, Magnetic resonance imaging, Mesenchymal Stem Cells, 021001 nanoscience & nanotechnology, Image Enhancement, Magnetic Resonance Imaging, 3. Good health, chemistry, Cell Tracking, Blood Vessels, Stem cell, 0210 nano-technology, Iron oxide nanoparticles, Biomedical engineering
Abstract

International audience; Recent advances in cell therapy and tissue engineering opened new windows for regenerative medicine, but still necessitate innovative noninvasive imaging technologies. We demonstrate that high-resolution magnetic resonance imaging (MRI) allows combining cellular-scale resolution with the ability to detect two cell types simultaneously at any tissue depth. Two contrast agents, based on iron oxide and gadolinium oxide rigid nanoplatforms, were used to "tattoo" endothelial cells and stem cells, respectively, with no impact on cell functions, including their capacity for differentiation. The labeled cells' contrast properties were optimized for simultaneous MRI detection: endothelial cells and stem cells seeded together in a polysaccharide-based scaffold material for tissue engineering appeared respectively in black and white and could be tracked, at the cellular level, both in vitro and in vivo. In addition, endothelial cells labeled with iron oxide nanoparticles could be remotely manipulated by applying a magnetic field, allowing the creation of vessel substitutes with in-depth detection of individual cellular components.

Published
2013

9. Localization and relative quantification of carbon nanotubes in cells with multispectral imaging flow cytometry

Author

Cécilia Ménard-Moyon, Claire Wilhelm, Nathalie Luciani, Alberto Bianco, Florence Gazeau, Iris Marangon, Nicole Boggetto, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut Jacques Monod (IJM (UMR_7592)), Immunologie et chimie thérapeutiques (ICT), Cancéropôle du Grand Est-Centre National de la Recherche Scientifique (CNRS), Region Ile de France (contract no E539), CNRS, and Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)

Subjects
chemistry, metabolism, Materials science, analysis, General Chemical Engineering, [SDV]Life Sciences [q-bio], Multispectral image, Nanoparticle, 02 engineering and technology, Carbon nanotube, [SDV.BC]Life Sciences [q-bio]/Cellular Biology, General Biochemistry, Genetics and Molecular Biology, law.invention, Flow cytometry, Nanomaterials, 03 medical and health sciences, law, medicine, Human Umbilical Vein Endothelial Cells, Humans, Nanotechnology, Cells, Cultured, 030304 developmental biology, Fluorescent Dyes, instrumentation, methods, 0303 health sciences, bioengineering, General Immunology and Microbiology, medicine.diagnostic_test, business.industry, Scattering, Nanotubes, Carbon, General Neuroscience, Colocalization, cellular uptake, bio-nano-interactions, imaging flow cytometry, 021001 nanoscience & nanotechnology, Flow Cytometry, Fluorescence, Optoelectronics, Carbon Nanotubes, Chimie/Chimie thérapeutique, Issue 82, cell trafficking, 0210 nano-technology, business, Fluorescein-5-isothiocyanate
Abstract

Carbon-based nanomaterials, like carbon nanotubes (CNTs), belong to this type of nanoparticles which are very difficult to discriminate from carbon-rich cell structures and de facto there is still no quantitative method to assess their distribution at cell and tissue levels. What we propose here is an innovative method allowing the detection and quantification of CNTs in cells using a multispectral imaging flow cytometer (ImageStream, Amnis). This newly developed device integrates both a high-throughput of cells and high resolution imaging, providing thus images for each cell directly in flow and therefore statistically relevant image analysis. Each cell image is acquired on bright-field (BF), dark-field (DF), and fluorescent channels, giving access respectively to the level and the distribution of light absorption, light scattered and fluorescence for each cell. The analysis consists then in a pixel-by-pixel comparison of each image, of the 7,000-10,000 cells acquired for each condition of the experiment. Localization and quantification of CNTs is made possible thanks to some particular intrinsic properties of CNTs: strong light absorbance and scattering; indeed CNTs appear as strongly absorbed dark spots on BF and bright spots on DF with a precise colocalization. This methodology could have a considerable impact on studies about interactions between nanomaterials and cells given that this protocol is applicable for a large range of nanomaterials, insofar as they are capable of absorbing (and/or scattering) strongly enough the light. journal article research support, non-u.s. gov't video-audio media 2013 Dec 12 2013 12 12 imported The video component of this article can be found at http://www.jove.com/video/50566/

Published
2013

10. In vivo biodistribution and biological impact of injected carbon nanotubes using magnetic resonance techniques

Author

Yannick Crémillieux, Achraf Al Faraj, Ghislaine Lacroix, Michael Levy, Nathalie Luciani, Florence Fauvelle, Emmanuelle Canet-Soulas, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Biophysique Cellulaire et Moléculaire, Centre Recherche Service Santé Armée, Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Institut National de l'Environnement Industriel et des Risques (INERIS), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL)

Subjects
Male, Magnetic Resonance Spectroscopy, Gene Expression, Pharmaceutical Science, MAGNETIC RESONANCE IMAGING, HIGH RESOLUTION MAGIC ANGLE SPINNING, 02 engineering and technology, Kidney, Spectrum Analysis, Raman, law.invention, Rats, Sprague-Dawley, Coating, International Journal of Nanomedicine, law, Drug Discovery, Tissue Distribution, Original Research, Drug Carriers, 0303 health sciences, General Medicine, 021001 nanoscience & nanotechnology, 3. Good health, Nanomedicine, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Injections, Intravenous, [SDE]Environmental Sciences, 0210 nano-technology, Drug carrier, Biodistribution, Materials science, Iron, Biophysics, Bioengineering, Nanotechnology, Carbon nanotube, engineering.material, Biomaterials, 03 medical and health sciences, In vivo, Animals, Tissue distribution, DNA Primers, 030304 developmental biology, Base Sequence, Nanotubes, Carbon, Spectrophotometry, Atomic, Organic Chemistry, Rats, In vivo biodistribution, engineering, SINGLE-WALLED CARBON NANOTUBES, Spleen
Abstract

Achraf Al Faraj1,2, Florence Fauvelle3, Nathalie Luciani4, Ghislaine Lacroix5, Michael Levy4, Yannick Crémillieux1, Emmanuelle Canet-Soulas1Université Lyon1, Créatis-LRMN, Lyon, France; 2King Saud University, College of Applied Medical Sciences, Radiological Sciences Department, Riyadh, Kingdom of Saudi Arabia; 3CRSSA, Biophysique Cellulaire et Moléculaire, Laboratoire de RMN, La Tronche, France; 4Université Paris7-Paris Diderot, Matières et Systèmes Complexes, Paris, France; 5Institut National de l’Environnement et des Risques Industriels, Verneuil-en-Halatte, FranceBackground: Single-walled carbon nanotubes (SWCNT) hold promise for applications as contrast agents and target delivery carriers in the field of nanomedicine. When administered in vivo, their biodistribution and pharmacological profile needs to be fully characterized. The tissue distribution of carbon nanotubes and their potential impact on metabolism depend on their shape, coating, and metallic impurities. Because standard radiolabeled or fluorescently-labeled pharmaceuticals are not well suited for long-term in vivo follow-up of carbon nanotubes, alternative methods are required.Methods: In this study, noninvasive in vivo magnetic resonance imaging (MRI) investigations combined with high-resolution magic angle spinning (HR-MAS), Raman spectroscopy, iron assays, and histological analysis ex vivo were proposed and applied to assess the biodistribution and biological impact of intravenously injected pristine (raw and purified) and functionalized SWCNT in a 2-week longitudinal study. Iron impurities allowed raw detection of SWCNT in vivo by susceptibility-weighted MRI.Results: A transitional accumulation in the spleen and liver was observed by MRI. Raman spectroscopy, iron assays, and histological findings confirmed the MRI readouts. Moreover, no acute toxicological effect on the liver metabolic profile was observed using the HR-MAS technique, as confirmed by quantitative real-time polymerase chain reaction analysis.Conclusion: This study illustrates the potential of noninvasive MRI protocols for longitudinal assessment of the biodistribution of SWCNT with associated intrinsic metal impurities. The same approach can be used for any other magnetically-labeled nanoparticles.Keywords: single-walled carbon nanotubes, magnetic resonance imaging, high resolution magic angle spinning

Published
2011

11. Long term in vivo biotransformation of iron oxide nanoparticles

Author

Alain Luciani, Sophie Lotersztajn, Nidhi Vats, Florence Gazeau, Claire Wilhelm, Guillaume Wang, Vanessa Deveaux, Francois Gendron, Dan Elgrabli, Nathalie Luciani, Sophie Chat, Cécile Factor, Christine Péchoux, Damien Alloyeau, Michael Levy, Matière et Systèmes Complexes (MSC), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Matériaux et Phénomènes Quantiques (MPQ (UMR_7162)), Institut National de l'Environnement Industriel et des Risques (INERIS), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Groupe d'étude des proliférations lymphoïdes (GPL), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Nanosciences de Paris (INSP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Laboratoire Guerbet / Guerbet Research, Imagerie Médicale, Groupe Henri Mondor Albert Chenevier, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Guerbet, Génomique et Physiologie de la Lactation (UR 1196), and Institut National de la Recherche Agronomique (INRA)

Subjects
Male, Materials science, Biophysics, Iron oxide, Bioengineering, Nanotechnology, Context (language use), BIODEGRADATION, 02 engineering and technology, 010402 general chemistry, 01 natural sciences, Ferric Compounds, Biomaterials, chemistry.chemical_compound, Mice, Biotransformation, Microscopy, Electron, Transmission, NANOTOXICITY, NANOPARTICLES, Animals, NANOMAGNETISM, biology, Electron Spin Resonance Spectroscopy, IRON OXIDE, CONTRAST AGENT, 021001 nanoscience & nanotechnology, 0104 chemical sciences, Ferritin, chemistry, Mechanics of Materials, Nanotoxicology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, [SDE]Environmental Sciences, Ceramics and Composites, biology.protein, Nanomedicine, 0210 nano-technology, Iron oxide nanoparticles, Superparamagnetism
Abstract

International audience; The long term outcome of nanoparticles in the organism is one of the most important concerns raised by the development of nanotechnology and nanomedicine. Little is known on the way taken by cells to process and degrade nanoparticles over time. In this context, iron oxide superparamagnetic nanoparticles benefit from a privileged status, because they show a very good tolerance profile, allowing their clinical use for MRI diagnosis. It is generally assumed that the specialized metabolism which regulates iron in the organism can also handle iron oxide nanoparticles. However the biotransformation of iron oxide nanoparticles is still not elucidated. Here we propose a multiscale approach to study the fate of nanomagnets in the organism. Ferromagnetic resonance and SQUID magnetization measurements are used to quantify iron oxide nanoparticles and follow the evolution of their magnetic properties. A nanoscale structural analysis by electron microscopy complements the magnetic follow-up of nanoparticles injected to mice. We evidence the biotransformation of superparamagnetic maghemite nanoparticles into poorly-magnetic iron species probably stored into ferritin proteins over a period of three months. A putative mechanism is proposed for the biotransformation of iron-oxide nanoparticles

Published
2011

12. High-Resolution 1.5-Tesla Magnetic Resonance Imaging for Tissue-Engineered Constructs: A Noninvasive Tool to Assess Three-Dimensional Scaffold Architecture and Cell Seeding

Author

Jean-Christophe Ginefri, Catherine Le Visage, Didier Letourneur, Luc Darrasse, Claire Wilhelm, Nathalie Luciani, Marie Poirier-Quinot, Guillaume Frasca, Florence Gazeau, Unite de recherche en résonance magnétique médicale (URRMM), Université Paris-Sud - Paris 11 (UP11), Matière et Systèmes Complexes (MSC (UMR_7057)), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biologie physico-chimique des protéines membranaires (LBPC-PM (UMR_7099)), Institut de biologie physico-chimique (IBPC), Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), and Institut de biologie physico-chimique (IBPC (FR_550))

Subjects
Materials science, Cell Transplantation, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Cell seeding, [SDV]Life Sciences [q-bio], Cell Culture Techniques, Biomedical Engineering, Medicine (miscellaneous), Nanoparticle, High resolution, Biocompatible Materials, Bioengineering, 02 engineering and technology, Ferric Compounds, Mice, 03 medical and health sciences, Imaging, Three-Dimensional, medicine, Animals, Humans, Cells, Cultured, 030304 developmental biology, Three dimensional scaffolds, 0303 health sciences, Tissue engineered, Tissue Engineering, Tissue Scaffolds, medicine.diagnostic_test, Cell growth, Mesenchymal stem cell, Mesenchymal Stem Cells, Magnetic resonance imaging, 021001 nanoscience & nanotechnology, Magnetic Resonance Imaging, Mice, Inbred C57BL, Radiography, Nanoparticles, [SDV.IB]Life Sciences [q-bio]/Bioengineering, 0210 nano-technology, Biomedical engineering
Abstract

International audience; Tissue-engineered scaffolds are made of biocompatible polymers with various structures, allowing cell seeding, growth, and differentiation. Noninvasive imaging methods are needed to study tissue-engineered constructs before and after implantation. Here, we show that high-resolution magnetic resonance imaging (MRI) performed on a clinical 1.5-T device is a reliable technique to assess three-dimensional structures of porous scaffolds and to validate cell-seeding procedures. A high-temperature superconducting detection coil was used to achieve a resolution of 30Â30Â30 mm 3 when imaging the scaffolds. Three types of structures with tuneable architectures were prepared from naturally derived polysaccharides and evaluated as scaffolds for mesenchymal stem cell (MSC) culture. To monitor cell seeding, MSCs were magnetically labeled using simple incubation with anionic citrate-coated iron-oxide nanoparticles for 30 min. Iron uptake was quantified using single-cell magnetophoresis, and cell proliferation was checked for 7 days after labeling. Three-dimensional (3D) microstructures of scaffolds were assessed using MRI, revealing lamellar or globular porous organization according to the scaffold preparation process. MSCs with different iron load (5, 12 and 31 pg of iron per cell) were seeded on scaffolds at low density (132 cells=mm 3) and detected on 3D gradient-echo MR images according to phase distortions and areas of intensely low signal, whose size increased with cell iron load and echo time. Overall signal loss in the scaffold correlated with the number of seeded cells and their iron load. Different organizations of cells were observed depending on the scaffold architecture. After subcutaneous implantation in mice, scaffolds seeded with labeled cells could be distinguished in vivo from scaffold with nonlabeled cells by observation of signal and phase heterogeneities and by measuring the global signal loss. High-resolution 1.5-T MRI combined with efficient intracellular contrast agents shows promise for noninvasive 3D visualization of tissue-engineered constructs before and after in vivo implantation.

Published
2010

13. Reactivity of the monocyte/macrophage system to superparamagnetic anionic nanoparticles

Author

Nathalie Luciani, Florence Gazeau, Claire Wilhelm, Matière et Systèmes Complexes (MSC (UMR_7057)), Centre National de la Recherche Scientifique (CNRS)-Université Paris Diderot - Paris 7 (UPD7), Unité d'Océanographie Chimique, Interfacultary Center for Marine Research (MARE), Université de Liège-Université de Liège, Laboratoire d'océanographie de Villefranche (LOV), Observatoire océanologique de Villefranche-sur-mer (OOVM), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Unité d'Océanographie Chimique (B5), MARE, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire océanologique de Villefranche-sur-mer (OOVM), and Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)

Subjects
Cell, Population, 02 engineering and technology, Cell membrane, 03 medical and health sciences, Nuclear magnetic resonance, Materials Chemistry, medicine, Extracellular, Macrophage, [PHYS.MECA.BIOM]Physics [physics]/Mechanics [physics]/Biomechanics [physics.med-ph], education, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, 0303 health sciences, education.field_of_study, Chemistry, [SPI.MECA.BIOM]Engineering Sciences [physics]/Mechanics [physics.med-ph]/Biomechanics [physics.med-ph], General Chemistry, 021001 nanoscience & nanotechnology, medicine.anatomical_structure, Biophysics, Magnetic nanoparticles, 0210 nano-technology, Drug carrier, Superparamagnetism
Abstract

Nano-scale magnetic materials are increasingly being used in the biomedical field for medical imaging, drug-delivery, magnetic sorting, and therapeutic hyperthermia. In particular, magnetic cell labelling offer attractive possibilities for MRI cell imaging, allowing the tracking of a cell population in living animals. Understanding of the interaction of nanoparticles with cells is then of paramount importance. Here, we characterize the uptake of anionic magnetic nanoparticles by THP1 monocytes and derived macrophages. The incorporation of nanoparticles was assessed by electron microscopy. Cell capture was then quantitated as a function of incubation time and extracellular iron. A simple binding–internalisation mechanism allowed modelling all uptake curves, leading to the affinity constants, the maximal mass that can adsorb on the cell membrane, the internalisation time constants and capacities. Though the adsorption step was comparable for monocytes and macrophages, the latter exhibited a more than ten times higher endocytotic activity. For both cell types, we report an excellent efficiency of the magnetic label, with a maximum load of 6 pgFecell−1 in monocytes and almost 50 pgFecell−1 in derived macrophages. Finally, we demonstrated that endocytosed nanoparticles did not affect differentiation of labelled monocytes into macrophages.

Published
2009

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