|Department:||School of Molecular Biosciences|
|Office:||Biotechnology/Life Sciences 233|
|Mailing Address:||PO Box 647520|
Pullman, WA 99164-7520
Mechanisms that will induce regeneration in skin wounds utilizing fibroblast lineages
The biological process of wound healing in the skin normally results in the formation of a scar, which isn't a problem if they are small (minor cuts). However, individuals with deep wounds that cover large portions their body would significantly benefit from a way to fully regenerate skin while inhibiting scar formation. This is because current medical procedures do not have the ability to reform hair follicles and sweat glands from deep wounds, such as those that occur during a major surgery. There is also a problem with skin grafts because they only can replace the outer-most layers of cells called the epidermis. The loss of hair follicles and sweat glands in wounded skin inhibits also affects the cosmetic makeup of skin.
The story of scar formation in the skin starts with an infliction of a wound, which is essentially a newly created hole in the tissue that becomes filled with many different cell types. This includes migrating blood, mesenchymal cells (fibroblasts), epithelial cells which interact to form new tissue which rebuilds new tissue within the hole. The spatial and temporal interactions during this process is critical for repairing the tissue, which normally results in the formation of a scar. Interestingly, it is possible to modulate the repair process, thereby influencing the quality of repair, by controlling epithelial cells and fibroblasts as they enter the blood clot.
We have recently discovered that , by controlling the nature of a fibroblasts before and after wounding in the skin, we can influence hair regeneration in the wound, which represents an essential part of skin regeneration (Driskell et al. 2013 - Nature). In addition, we found that the reason why scars normally lack hair is because adult skin lacks fibroblast subtypes that support hair follicle development. Furthermore, we have also found why young skin heals better than older skin. This is because the critical cells required for hair follicle neogenesis can be found in normal young (neonatal) dermis of mice or can be induced to replicate by increasing Wnt signalling in the epidermis before wounding (Driskell et al. 2013; Rognoni et al. 2016). Despite these advances, our findings revealed a need to investigate the mechanisms that control the type of hair follicle regeneration in the wound and its ability to function.
Salz L, and Driskell RR. (2017) The Sox2: GFP+/- knock in mouse model does not faithfully recapitulate Sox2 expression in skin. Exp Dermatol. doi: 10.1111/exd.13396.
Salz L, and Driskell RR. (2017) A novel processing and imaging protocol for thick three-dimensional cross-sections of skin called “Horizontal Whole Mount”. Journal of Visualized Experiments In Press
Rognoni E, Gomez, Pisco AO, Rawlins EL, Watt FM, and Driskell RR. (2016) Inhibition of b-catenin signaling in dermal fibroblasts enhances hair follicle regeneration during wound healing. Development 143:2522-2535; doi 10.1242/dev.131797.
Mastrogiannaki M, Lichtenberger BM, Reimer A, Collins CA, Driskell RR, and Watt FM. (2016) b-catenin stabilization in skin fibroblasts causes fibrotic lesions by preventing adipocyte differentiation of the reticular dermis. J. Invest. Dermatol. 136(6):1130-42. doi: 10.1016/j.jid2016.01.036.
Kaushal G, Rognoni E, Lichtenberger BM, Driskell RR, Kretzschmar K, Hoste E, and Watt FM. (2015) Fate of Prominin-1 expressing dermal papilla cells during homeostasis, wound healing and Wnt activation. J. Invest. Dermatol. 135(12):2926-34. Doi: 10.1038/jid.2015.319