Stretching skin without breaking it
How can skin expand while maintaining its structure and protective barrier function? This is a key question in biology, but it is also central to clinical practices such as reconstructive surgery, where controlled stretching is used to generate additional skin. A new transnational collaborative study, published in Nature Communications and coordinated by Associate Professor Mariaceleste Aragona’s group at reNEW Copenhagen, uncovers some of the fundamental cellular mechanisms underlying this process. The work involved key contributions from the groups of Associate Professor Alejandro Sifrim at KU Leuven, Belgium and Associate Professor Elena Enzo from the Center for Regenerative Medicine in Modena, Italy.
“Successful skin expansion depends on a precise coordination between the skin’s two main layers: the epidermis that contains the stem cells responsible for generating new skin cells, and the dermis, which provides structural support through fibroblast cells,” explains Associate Professor Mariaceleste Aragona.
While it was already known that stretching stimulates epidermal stem cells in the outer skin layer to self-renew and produce more skin, the role of the underlying dermis has remained unclear.
Using mouse models, advanced lineage tracing, and single-cell RNA sequencing, the research teams created a detailed map of skin cell behaviour during stretch-induced expansion. They found that the fibroblast cells in the dermis undergo a shift to a more immature state where they proliferate more, reduce collagen production, and remodel the extracellular matrix (ECM). Altogether, this creates a softer, more dynamic environment that better supports the epidermal stem cells and thus enables continued skin growth while preserving barrier function. The findings were validated using an in vitro skin graft system, showing that this fibroblast behaviour is also required to support human skin stem cells during expansion.
“Skin expansion depends on coordinated interactions between the different layers. The supporting fibroblasts must adopt a more immature, regenerative state to create an environment that allows epidermal stem cells to expand safely. It is not just a single molecule driving the process, but rather a combination of ECM remodelling proteins and mechanical properties,” Aragona concludes.
This new insight into the basic cell biology of the process is clinically relevant, as stretch-induced skin expansion is widely used in reconstructive surgery to generate additional tissue. It opens opportunities to improve skin graft engineering techniques and advance regenerative skin therapies.