Project description
Imaging the process of scar formation
In humans, wound repair often leads to the formation of fibrous tissue known as scar. Scar phenotype varies and depends on the type of injury, the anatomic location, age, and gender. The key objective of the EU-funded ScarLessWorld project is to shed light on the process of scar formation whose prevention represents a clinical challenge. Researchers are working under the hypothesis that scarring and regeneration depend on the tissue composition in specific fibroblasts. Using whole-animal live imaging and cell tracking, they will determine the structural and genetic changes that take place during scarring, paving the way for novel regenerative medicine strategies.
Objective
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.
Fields of science
Programme(s)
Funding Scheme
ERC-COG - Consolidator GrantHost institution
85764 Neuherberg
Germany