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

Project Information

ScarLessWorld

Grant agreement ID: 819933

DOI

10.3030/819933

Project closed

EC signature date 13 March 2019

Start date 1 April 2019

End date 31 March 2024

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 997 890,00

EU contribution

€ 1 997 890,00

Coordinated by

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)

Reporting period: 2023-10-01 to 2024-03-31

Summary of the context and overall objectives of the project

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.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

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.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

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