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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.

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

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

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 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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