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Rethyming SIGNED

Rebuilding the human thymus to create a tolerising system for allogeneic tissue and organ transplantation

Total Cost €

0

EC-Contrib. €

0

Partnership

0

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 Rethyming project word cloud

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

rejection    possibility    fashion    stem    vascular    breakthrough    epithelial    fresh    threatening    delivered    maintaining    natural    extracellular    induce    cell    lymphocytes    clinical    perfusion    vivo    thymi    complexity    phenotypic    translation    rebuilding    suppressive    induction    deep    immunity    cells    rapid    cultured    technologies    thymus    competence    differentiation    takes    thymic    epithelializing    immune    subsequently    pathogens    ex    antigens    scaffolds    immunosuppression    combining    epithelialization    decellularization    customized    structures    became    tecs    cancer    central    free    interaction    mature    bioreactor    immature    complications    revolutionized    scaffold    donor    animal    organ    matrix    selectively    re    achievement    mechanisms    transplantation    irreversibly    diseased    multidisciplinary    first    tregs    pig    mismatched    cellular    proof    biology    therapy    cultivated    bioengineering    expressed    performed    human    life    context    specified    medicine    frequency    dissect    optimized    preserved    replace    hla    prepared    tolerance    functional    immunosuppressive    antigen   

Project "Rethyming" data sheet

The following table provides information about the project.

Coordinator
UNIVERSITY COLLEGE LONDON 

Organization address
address: GOWER STREET
city: LONDON
postcode: WC1E 6BT
website: n.a.

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 United Kingdom [UK]
 Total cost 1˙480˙416 €
 EC max contribution 1˙480˙416 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-STG
 Funding Scheme ERC-STG
 Starting year 2015
 Duration (year-month-day) from 2015-07-01   to  2021-06-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    UNIVERSITY COLLEGE LONDON UK (LONDON) coordinator 1˙480˙416.00

Map

 Project objective

Organ transplantation has revolutionized medicine as it became possible to replace an irreversibly diseased organ. However, the immune suppressive therapy to avoid rejection is associated to life-threatening complications. Finding a way to selectively induce tolerance to donor antigens, while maintaining immunity to pathogens and cancer antigens would represent a major breakthrough in medicine with the achievement of immunosuppression-free organ transplantation. During development and early life immune T cell competence and central tolerance are specified in the thymus; thus I aim to dissect the complexity of this organ by rebuilding it in a controlled fashion ex vivo. In a first step, a natural scaffold will be prepared from fresh human and animal thymi by perfusion decellularization; subsequently cultivated human thymic epithelial cells (TECs) will be used for re-epithelialization of the a-cellular scaffolds. Finally, immature lymphocytes from an HLA-mismatched donor will be delivered to the thymus-scaffolds through the preserved vascular extracellular matrix structures and cultured in a customized bioreactor in optimized conditions for T cell differentiation and tolerance induction. Detailed phenotypic and functional analyses will be performed to identify the frequency of mature T cell subsets, including Tregs, and assess the level of tolerance to the HLA antigens expressed by TECs. Finally, the possibility of re-epithelializing scaffolds with pig TECs will allow testing its interaction in vivo in the context of organ transplantation, providing the very first proof of principle that it may be possible to achieve antigen-specific tolerance and avoid rejection without the need for generic immunosuppressive therapy.

Overall, this project takes a multidisciplinary approach to the study of tolerance by combining stem cell biology, bioengineering technologies, a deep knowledge of immunity and tolerance mechanisms in transplantation for a rapid clinical translation.

 Publications

year authors and title journal last update
List of publications.
2018 Robert E Hynds, Paola Bonfanti, Sam M Janes
Regenerating human epithelia with cultured stem cells: feeder cells, organoids and beyond
published pages: 139-150, ISSN: 1757-4676, DOI: 10.15252/emmm.201708213
EMBO Molecular Medicine 10/2 2019-04-25

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