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A WORLD WITHOUT SCARS: Regenerating wounded skin rather than patching with scars

Descrizione del progetto

Imaging del processo di formazione delle cicatrici

Negli esseri umani, la riparazione delle ferite comporta spesso la formazione di tessuto fibroso noto come cicatrice. Il fenotipo delle cicatrici varia e dipende dal tipo di lesione, dalla posizione anatomica, dall’età e dal sesso. L’obiettivo chiave del progetto ScarLessWorld, finanziato dall’UE, è quello di far luce sul processo di formazione delle cicatrici, la cui prevenzione rappresenta una sfida clinica. I ricercatori stanno lavorando all’ipotesi che la cicatrizzazione e la rigenerazione dipendano dalla composizione del tessuto in fibroblasti specifici. Utilizzando l’imaging dal vivo su animali interi e il monitoraggio delle cellule, determineranno i cambiamenti strutturali e genetici che avvengono durante la cicatrizzazione, aprendo la strada a strategie innovative di medicina rigenerativa.

Obiettivo

Scars are a mystery. They rarely develop in lower vertebrates, where the norm is a complete regeneration of damaged tissues, but are frequent in mammals including humans. Scar phenotypes depend on different injury types, anatomic locations, age, gender and species. The natural diversity of scars includes rare cases, where damaged tissues regenerate without scarring. The scar/regeneration decision remains unresolved and scar prevention is a clinical challenge.
Current research has been held up by conceptual and operational bottlenecks. The current conceptual notion comes from experiments showing that scarring depends on the internal environment of the injured organ. I challenged this notion by uncovering specialized fibroblast cell lineages that regenerate connective tissues without scars, anywhere, anytime. My hypothesis is that the decision to scar/regenerate lies in the compositions of specific fibroblast types. To further study this theory I had to resolve a second bottleneck, the current lack of assays that display the full complexity of scarring and regeneration. I have thus developed innovative technological approaches (four novel tools) that allow whole-animal live imaging, tracking and gene modification of fibroblasts.
Building on these innovative tools and my expertise in cell lineages as linchpins of this proposal, I aim to: (1) catalogue the repertoires of dermal fibroblast lineages, (2) image their dynamics during scarring/regeneration (3) identify the decision-making genes for scarring/regeneration in actual skin tissues, and finally (4) translate our findings from mouse to human skin. This new notion that specialized fibroblast lineages drive scarring/regeneration, combined with the technology breakthroughs, will greatly advance our current understanding of scar formation, which is a significant worldwide biomedical problem, creating new research avenues for regenerative medicine far beyond the current state-of-the-art.

Meccanismo di finanziamento

ERC-COG - Consolidator Grant

Coordinatore

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Contribution nette de l'UE
€ 1 997 890,00
Indirizzo
Ingolstadter landstrasse 1
85764 Neuherberg
Germania

Mostra sulla mappa

Regione
Bayern Oberbayern München, Landkreis
Tipo di attività
Research Organisations
Collegamenti
Altri finanziamenti
€ 0,00

Beneficiari (1)