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PARAGEN SIGNED

Biomaterials with incorporated MSC-secreted PARAcrine molecules for bone reGENeration

Total Cost €

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EC-Contrib. €

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Partnership

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 PARAGEN project word cloud

Explore the words cloud of the PARAGEN project. It provides you a very rough idea of what is the project "PARAGEN" about.

media    death    collect    endothelial    act    huge    consuming    mediators    benefit    tissue    secreted    implantation    femoral    devoid    off    autologous    induce    defects    cells    normoxia    polyelectrolyte    release    engineering    treatment    risk    donor    permits    osteoclasts    biocompatibility    phosphate    transfer    countless    successfully    secretion    situ    pem    hypoxia    potent    die    rejection    vitro    variability    extracellular    orthopaedics    regeneration    biphasic    macrophages    calcium    patient    promise    measured    cell    implanting    carry    subcutis    mesenchymal    prepare    vivo    stromal    ceramics    time    pf    dependent    cultured    layering    paracrine    tested    cm    themselves    critical    patients    kinetics    vesicles    clinical    segmented    nude    benefits    msc    functionalized    shelf    effectors    therapy    bone    monocytes    costly    onto    overcome    straightforward    circumvent    loaded    seems    immense    sites    conditioned    cytokines    shortly    mice    harness    therapeutic    biomaterials   

Project "PARAGEN" data sheet

The following table provides information about the project.

Coordinator
INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE 

Organization address
address: RUE DE TOLBIAC 101
city: PARIS
postcode: 75654
website: www.inserm.fr

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country France [FR]
 Total cost 246˙668 €
 EC max contribution 246˙668 € (100%)
 Programme 1. H2020-EU.1.3.2. (Nurturing excellence by means of cross-border and cross-sector mobility)
 Code Call H2020-MSCA-IF-2015
 Funding Scheme MSCA-IF-GF
 Starting year 2017
 Duration (year-month-day) from 2017-03-20   to  2020-03-19

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE FR (PARIS) coordinator 246˙668.00
2    PRESIDENT AND FELLOWS OF HARVARD COLLEGE US (CAMBRIDGE) partner 0.00

Map

 Project objective

Regeneration of bone defects remains a critical challenge in orthopaedics. Mesenchymal stromal cells (MSC) with biomaterials show huge promise for bone regeneration. However, MSC die shortly after implantation and act as mediators, by secretion of paracrine factors (PF), rather than effectors of bone formation. Importantly, it seems that delivery of cells themselves may not be required for therapeutic benefit. When MSC are cultured in vitro they release PF into their conditioned media (MSC-CM) including cytokines and extracellular vesicles. The goal of this project is to prepare novel biomaterials which are loaded with MSC-CM for in situ bone tissue engineering. PF secreted into MSC-CM during normoxia, hypoxia, and cell death will be measured. Biomaterials (biphasic calcium phosphate ceramics) will be functionalized with MSC-CM by using the polyelectrolyte multi-layering (PEM) method. The biocompatibility, release kinetics, and potential of MSC-CM loaded biomaterials for bone regeneration will be tested in vitro on cells involved in bone formation (MSC, monocytes, osteoclasts, macrophages, and endothelial cells) and in vivo by implanting the biomaterials in subcutis sites and segmented femoral defects in nude mice. Importantly, the delivery of MSC-CM can overcome the donor-dependent variability in bone formation associated with MSC cell therapy and permits a more straightforward transfer of this therapy to clinical treatment. Since MSC-CM is devoid of cells and doesn’t carry patient rejection risk, autologous MSC are not required. Therefore, selected MSC that successfully induce bone formation can be used to collect potent MSC-CM which can be loaded onto biomaterials for therapeutic use in countless patients. An ‘off-the-shelf’ product that could harness the benefits of MSC therapy but circumvent the costly and time consuming multi-step procedures involved with MSC implantation would be of immense interest to the bone regeneration field.

 Publications

year authors and title journal last update
List of publications.
2018 Clotilde Théry, Kenneth W Witwer, Elena Aikawa, Maria Jose Alcaraz, Johnathon D Anderson, Ramaroson Andriantsitohaina, Anna Antoniou, Tanina Arab, Fabienne Archer, Georgia K Atkin-Smith, D Craig Ayre, Jean-Marie Bach, Daniel Bachurski, Hossein Baharvand, Leonora Balaj, Shawn Baldacchino, Natalie N Bauer, Amy A Baxter, Mary Bebawy, Carla Beckham, Apolonija Bedina Zavec, Abderrahim Benmoussa, Anna C Berardi, Paolo Bergese, Ewa Bielska, Cherie Blenkiron, Sylwia Bobis-Wozowicz, Eric Boilard, Wilfrid Boireau, Antonella Bongiovanni, Francesc E Borràs, Steffi Bosch, Chantal M Boulanger, Xandra Breakefield, Andrew M Breglio, Meadhbh Á Brennan, David R Brigstock, Alain Brisson, Marike LD Broekman, Jacqueline F Bromberg, Paulina Bryl-Górecka, Shilpa Buch, Amy H Buck, Dylan Burger, Sara Busatto, Dominik Buschmann, Benedetta Bussolati, Edit I Buzás, James Bryan Byrd, Giovanni Camussi, David RF Carter, Sarah Caruso, Lawrence W Chamley, Yu-Ting Chang, Chihchen Chen, Shuai Chen, Lesley Cheng, Andrew R Chin, Aled Clayton, Stefano P Clerici, Alex Cocks, Emanuele Cocucci, Robert J Coffey, Anabela Cordeiro-da-Silva, Yvonne Couch, Frank AW Coumans, Beth Coyle, Rossella Crescitelli, Miria Ferreira Criado, Crislyn D’Souza-Schorey, Saumya Das, Amrita Datta Chaudhuri, Paola de Candia, Eliezer F De Santana, Olivier De Wever, Hernando A del Portillo, Tanguy Demaret, Sarah Deville, Andrew Devitt, Bert Dhondt, Dolores Di Vizio, Lothar C Dieterich, Vincenza Dolo, Ana Paula Dominguez Rubio, Massimo Dominici, Mauricio R Dourado, Tom AP Driedonks, Filipe V Duarte, Heather M Duncan, Ramon M Eichenberger, Karin Ekström, Samir EL Andaloussi, Celine Elie-Caille, Uta Erdbrügger, Juan M Falcón-Pérez, Farah Fatima, Jason E Fish, Miguel Flores-Bellver, András Försönits, Annie Frelet-Barrand, Fabia Fricke, Gregor Fuhrmann, Susanne Gabrielsson, Ana Gámez-Valero, Chris Gardiner, Kathrin Gärtner, Raphael Gaudin, Yong Song Gho, Bernd Giebel, Caroline Gilbert, Mario Gimona, Ilaria Giusti, Deborah CI Goberdhan, André Görgens, Sharon M Gorski, David W Greening, Julia Christina Gross, Alice Gualerzi, Gopal N Gupta, Dakota Gustafson, Aase Handberg, Reka A Haraszti, Paul Harrison, Hargita Hegyesi, An Hendrix, Andrew F Hill, Fred H Hochberg, Karl F Hoffmann, Beth Holder, Harry Holthofer, Baharak Hosseinkhani, Guoku Hu, Yiyao Huang, Veronica Huber, Stuart Hunt, Ahmed Gamal-Eldin Ibrahim, Tsuneya Ikezu, Jameel M Inal, Mustafa Isin, Alena Ivanova, Hannah K Jackson, Soren Jacobsen, Steven M Jay, Muthuvel Jayachandran, Guido Jenster, Lanzhou Jiang, Suzanne M Johnson, Jennifer C Jones, Ambrose Jong, Tijana Jovanovic-Talisman, Stephanie Jung, Raghu Kalluri, Shin-ichi Kano, Sukhbir Kaur, Yumi Kawamura, Evan T Keller, Delaram Khamari, Elena Khomyakova, Anastasia Khvorova, Peter Kierulf, Kwang Pyo Kim, Thomas Kislinger, Mikael Klingeborn, David J Klinke, Miroslaw Kornek, Maja M Kosanović, Árpád Ferenc Kovács, Eva-Maria Krämer-Albers, Susanne Krasemann, Mirja Krause, Igor V Kurochkin, Gina D Kusuma, Sören Kuypers, Saara Laitinen, Scott M Langevin, Lucia R Languino, Joanne Lannigan, Cecilia Lässer, Louise C Laurent, Gregory Lavieu, Elisa Lázaro-Ibáñez, Soazig Le Lay, Myung-Shin Lee, Yi Xin Fiona Lee, Debora S Lemos, Metka Lenassi, Aleksandra Leszczynska, Isaac TS Li, Ke Liao, Sten F Libregts, Erzsebet Ligeti, Rebecca Lim, Sai Kiang Lim, Aija Linē, Karen Linnemannstöns, Alicia Llorente, Catherine A Lombard, Magdalena J Lorenowicz, Ákos M Lörincz, Jan Lötvall, Jason Lovett, Michelle C Lowry, Xavier Loyer, Quan Lu, Barbara Lukomska, Taral R Lunavat, Sybren LN Maas, Harmeet Malhi, Antonio Marcilla, Jacopo Mariani, Javier Mariscal, Elena S Martens-Uzunova, Lorena Martin-Jaular, M Carmen Martinez, Vilma Regina Martins, Mathilde Mathieu, Suresh Mathivanan, Marco Maugeri, Lynda K McGinnis, Mark J McVey, David G Meckes, Katie L Meehan, Inge Mertens, Valentina R Minciacchi, Andreas Möller, Malene Møller Jørgensen, Aizea Morales-Kastresana, Jess Morhayim, François
Minimal information for studies of extracellular vesicles 2018 (MISEV2018): a position statement of the International Society for Extracellular Vesicles and update of the MISEV2014 guidelines
published pages: 1535750, ISSN: 2001-3078, DOI: 10.1080/20013078.2018.1535750
Journal of Extracellular Vesicles 7/1 2019-06-06
2017 Meadhbh A. Brennan, Audrey Renaud, Fabien Guilloton, Miryam Mebarki, Valerie Trichet, Luc Sensebé, Frederic Deschaseaux, Nathalie Chevallier, Pierre Layrolle
Inferior In Vivo Osteogenesis and Superior Angiogeneis of Human Adipose-Derived Stem Cells Compared with Bone Marrow-Derived Stem Cells Cultured in Xeno-Free Conditions
published pages: 2160-2172, ISSN: 2157-6564, DOI: 10.1002/sctm.17-0133
STEM CELLS Translational Medicine 6/12 2019-06-06
2019 Paul Humbert, Meadhbh Á. Brennan, Noel Davison, Philippe Rosset, Valérie Trichet, Frédéric Blanchard, Pierre Layrolle
Immune Modulation by Transplanted Calcium Phosphate Biomaterials and Human Mesenchymal Stromal Cells in Bone Regeneration
published pages: , ISSN: 1664-3224, DOI: 10.3389/fimmu.2019.00663
Frontiers in Immunology 10 2019-06-06

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