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

Informazioni relative al progetto

ScarLessWorld

ID dell’accordo di sovvenzione: 819933

DOI

10.3030/819933

Progetto chiuso

Data della firma CE 13 Marzo 2019

Data di avvio 1 Aprile 2019

Data di completamento 31 Marzo 2024

Finanziato da

• EXCELLENT SCIENCE - European Research Council (ERC)

Costo totale

€ 1 997 890,00

Contributo UE

€ 1 997 890,00

Coordinato da

HELMHOLTZ ZENTRUM MUENCHEN DEUTSCHES FORSCHUNGSZENTRUM FUER GESUNDHEIT UND UMWELT GMBH
Germany

Periodic Reporting for period 4 - ScarLessWorld (A WORLD WITHOUT SCARS: Regenerating wounded skin rather than patching with scars)

Periodo di rendicontazione: 2023-10-01 al 2024-03-31

Sintesi del contesto e degli obiettivi generali del progetto

How do scars form? Does Fascia have a function as a repository of mobile scar tissue

Abnormal scarring is a serious threat resulting in non-healing chronic wounds or fibrosis. Scars form when fibroblasts, a type of cell of connective tissue, reach wounded skin and deposit plugs of extracellular matrix. Until today, the question about the exact anatomical origin of these fibroblasts has not been answered. In order to find potential ways of influencing the scarring process, , aimed to finally find an answer. As it was already known that all scars derive from a fibroblast lineage expressing the Engrailed-1 gene – a lineage not only present in skin, but also in fascia – the researchers intentionally tried to understand whether or not fascia might be the origin of fibroblasts.

Lavoro eseguito dall’inizio del progetto fino alla fine del periodo coperto dalla relazione e principali risultati finora ottenuti

Fibroblasts kit – ready to heal wounds
In order to find out, they used an array of techniques including genetic lineage tracing, anatomical fate mapping, and genetic ablation, a method which in selected cells leads to apoptosis, cell death. This extinguished the fascia fibroblasts. It was discovered that no matrix was incorporated into the wounds and only abnormal and unhealthy scars with major disadvantages were formed.

In another approach the team placed a porous film beneath the skin to prevent fascia fibroblasts from migrating upwards. This, however, led to chronic open wounds. The researchers concluded that fascia contains a specialized prefabricated kit of sentry fibroblasts, embedded within a movable sealant, that preassemble together all the cell types and matrix components needed to heal wounds. They are assuming that guided homing of fascia initiates the hallmark response to external and internal injuries.

Progressi oltre lo stato dell’arte e potenziale impatto previsto (incluso l’impatto socioeconomico e le implicazioni sociali più ampie del progetto fino ad ora)

Scarring ensures survival
The new findings are important in context of ensuring survival: In mammals scarring injury induces a universal fibrotic tissue response that quickly patches wounds with scars – and thus prevents infection and bleeding to death. The hitherto tenet in wound repair was that scars form de novo by fibroblasts depositing extracellular matrix at sites of injury. With this study, the researchers could proof that scars originate from reservoirs of matrix jelly that are dragged into open wounds by sentry fibroblasts embedded in the fascia. These novel findings contradict current paradigms of how wounds repair.

New methods of scar less regenerative healing
The knowledge that fascia is the origin of scars and the finding of new mechanisms of wound repair provide a novel therapeutic space to curtail pathological fibrotic responses and induce scar less regenerative healing across a range of medical settings.

The findings of our research give fascia tissue a new role for future science. This will shift the attention of the scientific community to not only to look at fibroblasts in the dermis but also at native cells in the fascia when researching on wound healing,

fascia-cells-green-rising-into-dermal-open-wounds-dragging-their-surrounding-matrix-magenta-nature.jpg