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631 results on '"Letourneur, Didier"'

2. Erythrocyte-Inspired Discoidal Polymeric Nanoconstructs carrying Tissue Plasminogen Activator for the Enhanced Lysis of Blood Clots

Author

Colasuonno, Marianna, Palange, Anna Lisa, Aid, Rachida, Ferreira, Miguel, Mollica, Hilaria, Palomba, Roberto, Emdin, Michele, Del Sette, Massimo, Chauvierre, Cédric, Letourneur, Didier, and Decuzzi, Paolo

Subjects
Quantitative Biology - Quantitative Methods
Abstract

Tissue plasminogen activator (tPA) is the sole approved therapeutic molecule for the treatment of acute ischemic stroke. Yet, only a small percentage of patients could benefit from this life-saving treatment because of medical contraindications and severe side effects, including brain hemorrhage, associated with delayed administration. Here, a nano therapeutic agent is realized by directly associating the clinical formulation of tPA to the porous structure of soft discoidal polymeric nanoconstructs (tPA-DPNs). The porous matrix of DPNs protects tPA from rapid degradation, allowing tPA-DPNs to preserve over 70 % of the tPA original activity after 3 h of exposure to serum proteins. Under dynamic conditions, tPA-DPNs dissolve clots more efficiently than free tPA, as demonstrated in a microfluidic chip where clots are formed mimicking in vivo conditions. At 60 min post treatment initiation, the clot area reduces by half (57 + 8 %) with tPA-DPNs, whereas a similar result (56 + 21 %) is obtained only after 90 min for free tPA. In murine mesentery venules, the intravenous administration of 2.5 mg/kg of tPA-DPNs resolves almost 90 % of the blood clots, whereas a similar dose of free tPA successfully recanalize only about 40 % of the treated vessels. At about 1/10 of the clinical dose (1.0 mg/kg), tPA-DPNs still effectively dissolve 70 % of the clots, whereas free tPA works efficiently only on 16 % of the vessels. In vivo, discoidal tPA-DPNs outperform the lytic activity of 200 nm spherical tPA-coated nanoconstructs in terms of both percentage of successful recanalization events and clot area reduction. The conjugation of tPA with preserved lytic activity, the deformability and blood circulating time of DPNs together with the faster blood clot dissolution would make tPA-DPNs a promising nanotool for enhancing both potency and safety of thrombolytic therapies.

Published
2019

4. Bone Spheroid Development Under Flow Conditions with Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells in a 3D Porous Hydrogel Supplemented with Hydroxyapatite.

Author

El Hajj, Soukaina, Ntaté, Martial Bankoué, Breton, Cyril, Siadous, Robin, Aid, Rachida, Dupuy, Magali, Letourneur, Didier, Amédée, Joëlle, Duval, Hervé, and David, Bertrand

Subjects
LATTICE Boltzmann methods, MESENCHYMAL stem cells, CELL migration, HUMAN stem cells, ENDOTHELIAL cells
Abstract

Understanding the niche interactions between blood and bone through the in vitro co-culture of osteo-competent cells and endothelial cells is a key factor in unraveling therapeutic potentials in bone regeneration. This can be additionally supported by employing numerical simulation techniques to assess local physical factors, such as oxygen concentration, and mechanical stimuli, such as shear stress, that can mediate cellular communication. In this study, we developed a Mesenchymal Stem Cell line (MSC) and a Human Umbilical Vein Endothelial Cell line (HUVEC), which were co-cultured under flow conditions in a three-dimensional, porous, natural pullulan/dextran scaffold that was supplemented with hydroxyapatite crystals that allowed for the spontaneous formation of spheroids. After 2 weeks, their viability was higher under the dynamic conditions (>94%) than the static conditions (<75%), with dead cells central in the spheroids. Mineralization and collagen IV production increased under the dynamic conditions, correlating with osteogenesis and vasculogenesis. The endothelial cells clustered at the spheroidal core by day 7. Proliferation doubled in the dynamic conditions, especially at the scaffold peripheries. Lattice Boltzmann simulations showed negligible wall shear stress in the hydrogel pores but highlighted highly oxygenated zones coinciding with cell proliferation. A strong oxygen gradient likely influenced endothelial migration and cell distribution. Hypoxia was minimal, explaining high viability and spheroid maturation in the dynamic conditions. [ABSTRACT FROM AUTHOR]

Published
2024
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19. Fucoidan

Author

Maire, Murielle, primary, Chollet, Lucas, additional, Rolland, Lydia, additional, Letourneur, Didier, additional, Chauvierre, Cédric, additional, and Chaubet, Frédéric, additional

Published
2019
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24. Development of Novel Polysaccharide Membranes for Guided Bone Regeneration: In Vitro and In Vivo Evaluations.

Author

Ahmed Omar, Naïma, Roque, Jéssica, Galvez, Paul, Siadous, Robin, Chassande, Olivier, Catros, Sylvain, Amédée, Joëlle, Roques, Samantha, Durand, Marlène, Bergeaut, Céline, Bidault, Laurent, Aprile, Paola, Letourneur, Didier, Fricain, Jean-Christophe, and Fenelon, Mathilde

Subjects
BONE regeneration, DEXTRAN, GUIDED bone regeneration, MESENCHYMAL stem cells, POLYSACCHARIDES
Abstract

Introduction: Guided bone regeneration (GBR) procedures require selecting suitable membranes for oral surgery. Pullulan and/or dextran-based polysaccharide materials have shown encouraging results in bone regeneration as bone substitutes but have not been used to produce barrier membranes. The present study aimed to develop and characterize pullulan/dextran-derived membranes for GBR. Materials and methods: Two pullulan/dextran-based membranes, containing or not hydroxyapatite (HA) particles, were developed. In vitro, cytotoxicity evaluation was performed using human bone marrow mesenchymal stem cells (hBMSCs). Biocompatibility was assessed on rats in a subcutaneous model for up to 16 weeks. In vivo, rat femoral defects were created on 36 rats to compare the two pullulan/dextran-based membranes with a commercial collagen membrane (Bio-Gide®). Bone repair was assessed radiologically and histologically. Results: Both polysaccharide membranes demonstrated cytocompatibility and biocompatibility. Micro-computed tomography (micro-CT) analyses at two weeks revealed that the HA-containing membrane promoted a significant increase in bone formation compared to Bio-Gide®. At one month, similar effects were observed among the three membranes in terms of bone regeneration. Conclusion: The developed pullulan/dextran-based membranes evidenced biocompatibility without interfering with bone regeneration and maturation. The HA-containing membrane, which facilitated early bone regeneration and offered adequate mechanical support, showed promising potential for GBR procedures. [ABSTRACT FROM AUTHOR]

Published
2023
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34. A Preclinical Validation of Iron Oxide Nanoparticles for Treatment of Perianal Fistulizing Crohn’s Disease

Author

Cazelles, Antoine, primary, Collard, Maxime K., additional, Lalatonne, Yoann, additional, Doblas, Sabrina, additional, Zappa, Magaly, additional, Labiad, Camélia, additional, Cazals-Hatem, Dominique, additional, Maggiori, Léon, additional, Treton, Xavier, additional, Panis, Yves, additional, Jarry, Ulrich, additional, Desvallées, Thomas, additional, Eliat, Pierre-Antoine, additional, Pineau, Raphaël, additional, Motte, Laurence, additional, Letourneur, Didier, additional, Simon-Yarza, Teresa, additional, and Ogier-Denis, Eric, additional

Published
2022
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39. Histopathological evaluation of thrombus in patients presenting with stent thrombosis. A multicenter European study: a report of the prevention of late stent thrombosis by an interdisciplinary global European effort consortium†

Author

Riegger, Julia, Byrne, Robert A., Joner, Michael, Chandraratne, Sue, Gershlick, Anthony H., ten Berg, Jurrien M., Adriaenssens, Tom, Guagliumi, Giulio, Godschalk, Thea C., Neumann, Franz-Josef, Trenk, Dietmar, Feldman, Laurent J., Steg, Philippe Gabriel, Desmet, Walter, Alfonso, Fernando, Goodall, Alison H., Wojdyla, Roman, Dudek, Dariusz, Philippi, Vanessa, Opinaldo, Sheryl, Titova, Anna, Malik, Nikesh, Cotton, James, Jhagroe, Darshni A., Heestermans, Antonius A.C.M., Sinnaeve, Peter, Vermeersch, Paul, Valina, Christian, Schulz, Christian, Kastrati, Adnan, Massberg, Steffen, Adriaenssens, Tom, Buysschaert, Ian, Chausson, Mickaël, De Cock, Dries, Dens, Jo, Barbato, Emanuele, Desmet, Walter, Gautier, Sandrine, Vermeersch, Paul, Sinnaeve, Peter, Abergel, Helene, Feldman, Laurent, Jandrot-Perrus, Martine, Letourneur, Didier, Mangin, Pierre, Olivier, Véronique, Roques, Caroline, Byrne, Robert A., Chandraratne, Sue, Gratz, Matthias, Joner, Michael, Kastrati, Adnan, Kennerknecht, Elisabeth, Konrad, Ildiko, Koppara, Tobias, Massberg, Steffen, Neumann, Franz-Josef, Ntziachristos, Vasilis, Opinaldo, Sheryl, Philippi, Vanessa, Riegger, Julia, Rosenthal, Amir, Rzany, Alexander, Schulz, Christian, Steigerwald, Kristin, Tada, Tomohiso, Titova, Anna, Trenk, Dietmar, Valina, Christian, Vogelsang, Andreas, Xhepa, Erion, Bernelli, Chiara, Coccato, Micol, Guagliumi, Giulio, Komukai, Kenichi, Sirbu, Vasile, Kerch, Garry, Amoroso, Giovanni, ten Berg, Jurriën, Dewilde, Willem J.M., Godschalk, Thea C., Heestermans, Antonius A.C.M., Jhagroe, Darshni A., Wykrzykowska, Joanne J., Winkens, Mark H.M., Dudek, Dariusz, Rzeszutko, Łukasz, Wojdyla, Roman, Zasada, Wojciech, Alfonso, Fernando, Cuesta, Javier, Medina, Miguel, Berry, Colin, Cotton, James, Curzen, Nick, McEntegart, Margaret, Gerber, Robert, Gershlick, Anthony, Goodall, Alison H., Hetherington, Simon, Hill, Jonathan, Kelly, Damian, Malik, Nikesh, Oldroyd, Keith, Routledge, Helen, Shannon, Joanne, Suresh, Venkatesan, and Zahman, Azfar

Published
2016
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40. Nesting and fate of transplanted stem cells in hypoxic/ischemic injured tissues: The role of HIF1α/sirtuins and downstream molecular interactions.

Author

Barzegari, Abolfazl, Omidi, Yadollah, Gueguen, Virginie, Meddahi‐Pellé, Anne, Letourneur, Didier, and Pavon‐Djavid, Graciela

Subjects
HYPOXIA-inducible factor 1, STEM cells, MOLECULAR interactions, STEM cell niches, CELL anatomy, HYPOXIA-inducible factors, NESTS, CELL respiration
Abstract

The nesting mechanisms and programming for the fate of implanted stem cells in the damaged tissue have been critical issues in designing and achieving cell therapies. The fracture site can induce senescence or apoptosis based on the surrounding harsh conditions, hypoxia, and oxidative stress (OS). Respiration deficiency, disruption in energy metabolism, and consequently OS induction change the biophysical, biochemical, and cellular components of the native tissue. Additionally, the homeostatic molecular players and cell signaling might be changed. Despite all aforementioned issues, in the native stem cell niche, physiological hypoxia is not toxic; rather, it is vitally required for homing, self‐renewal, and differentiation. Hence, the key macromolecular players involved in the support of stem cell survival and re‐adaptation to a new dysfunctional niche must be understood for managing the cell therapy outcome. Hypoxia‐inducible factor 1‐alpha is the master transcriptional regulator, involved in the cell response to hypoxia and the adaptation of stem cells to a new niche. This protein is regulated by interaction with sirtuins. Sirtuins are highly conserved NAD+‐dependent enzymes that monitor the cellular energy status and modulate gene transcription, genome stability, and energy metabolism in response to environmental signals to modulate the homing and fate of stem cells. Herein, new insights into the nesting of stem cells in hypoxic–ischemic injured tissues were provided and their programming in a new dysfunctional niche along with the involved complex macromolecular players were critically discussed. [ABSTRACT FROM AUTHOR]

Published
2023
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41. Membranes for Guided Bone Regeneration: A Road from Bench to Bedside

Author

Aprile, Paola, Letourneur, Didier, Simon‐Yarza, Teresa, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Université Sorbonne Paris Nord, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Université Sorbonne Paris Nord, and LETOURNEUR, Didier

Subjects
Dental Implants, China, Bone Regeneration, [SDV]Life Sciences [q-bio], medical device regulations, Membranes, Artificial, [SDV] Life Sciences [q-bio], Biomaterials, Preclinical Study, Absorbable Implants, Guided Tissue Regeneration, Periodontal, Medical Device Regulation, Bone Tissue Engineering, Quality by Design, preclinical studies
Abstract

International audience; Bone resorption can negatively influence the osseointegration of dental implants. Barrier membranes for guided bone regeneration (GBR) are used to exclude nonosteogenic tissues from influencing the bone healing process. In addition to the existing barrier membranes available on the market, a growing variety of membranes for GBR with tailorable physicochemical properties are under preclinical evaluation. Hence, the aim of this review is to provide a comprehensive description of materials used for GBR and to report the main industrial and regulatory aspects allowing the commercialization of these medical devices (MDs). In particular, a summary of the main attributes defining a GBR membrane is reported along with a description of commercially available and under development membranes. Finally, strategies for the scaling-up of the manufacturing process and the regulatory framework of the main MD producers (USA, EU, Japan, China, and India) are presented. The description of the regulatory approval process of GBR membranes is representative of the typical path that medium- to high-risk MDs have to follow for an effective medical translation, which is of fundamental importance to increase the impact of biomedical research on public health.

Published
2020

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