Wound Repair

 
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Tissue repair is fundamental to our survival as tissues are challenged by recurrent damage. During mammalian skin repair, cells respond by migrating and proliferating to close the wound. To understand the coordination of cellular repair behaviors and their effects on homeostatic functions in a live mammal, we developed the ability to monitor tissue repair in real time and captured the spatiotemporal dynamics of individual epithelial behaviors by imaging wound re-epithelialization in live mice (Figure 1). 

Figure 1

Figure 1

By tracking cells over time and using a variety of genetic and pharmacological manipulations, we have been able to study how the interplay between repair behaviors, such as migration, leads to effective reconstruction of the epithelial tissue and the extent to which homeostatic processes such as differentiation and proliferation are affected during the repair process (Figure 2 & Movie). 

 
Figure 2

Figure 2

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Collectively, our studies have revealed 1) that both stem cells and differentiated cells migrate and functionally participate in wound repair, 2) that cells depart from a highly proliferative zone by directionally dividing towards the wound while collectively migrating, 3) that proliferation functions to pattern and restrict the recruitment of undamaged cells (Park, 2017).

Moving forward, we look to understand the relevant cross-talk that occurs during homeostatic conditions with neighboring populations such as mesenchymal and immune cells among others, which will provide tools for us to dissect their various contributions to de novo repair and to shed light on the critical cellular and signaling components that are required for tissue repair.