Projektbeschreibung
Dem Prozess der Narbenbildung auf der Spur
Beim Menschen lässt die Wundheilung häufig Fasergewebe entstehen – es bilden sich die sogenannten Narben. Das Erscheinungsbild einer Narbe variiert und ist von der Art der Verletzung, der anatomischen Lokalisation, dem Alter und dem Geschlecht abhängig. Hauptziel des EU-finanzierten Projekts ScarLessWorld ist die Erforschung des Prozesses der Narbenbildung, dessen Verhinderung oft eine klinische Herausforderung darstellt. Das Forschungsteam verfolgt die Hypothese, dass Narbenbildung und Regeneration von der Gewebezusammensetzung in spezifischen Fibroblasten abhängen. Anhand von Gesamtorganismus-Echtzeit-Bildgebung und Zellnachverfolgung werden die strukturellen und genetischen Veränderungen bestimmt, die im Verlauf der Narbenbildung stattfinden. Auf diese Weise wird neuartigen Strategien der regenerativen Medizin der Weg bereitet.
Ziel
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.
Wissenschaftliches Gebiet
Not validated
Not validated
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-COG - Consolidator GrantGastgebende Einrichtung
85764 Neuherberg
Deutschland