Screening for Drugs that Enhance Wound Healing by Spurring Greater Stem Cell Activity
The enhancement of stem cell activity is a very broad theme in medical research and development. It encompasses most present stem cell therapies, treatments that largely work through their effects on native stem cell populations, the parabiosis studies in search of blood-borne factors that both influence stem cells and change with age, and research such as the open access paper here, in which more traditional drug screening is used to search for candidates that can increase stem cell activity in a specific tissue of interest:
Advances in adult tissue stem cell biology have led to the idea that pharmacological activation of resident stem cells might represent a therapeutic strategy for tissue repair. Indeed, pharmacological candidates that regulate tissue stem cells have been identified. Here, we asked whether this is a viable strategy for skin repair. Skin is a complex tissue with many endogenous tissue stem cells. These include epidermal stem cells and a population of dermal stem cells called skin-derived precursors (SKPs). Cultured SKPs can clonally reconstitute the dermis and induce hair follicle morphogenesis, suggesting key roles for the endogenous precursors in dermal maintenance and hair follicle biology.Here, we have tested the idea that increasing the number or self-renewal of endogenous SKPs would enhance skin repair. To do so, we screened libraries of compounds that are used clinically in humans, looking for drugs that enhance SKP self-renewal. We identified two compounds, alprostadil and trimebutine maleate, that increased SKP self-renewal, likely by activating the MEK-ERK pathway. Both compounds enhanced wound healing when applied topically. These findings provide proof of principle for the idea that compounds that regulate SKPs in culture have therapeutic efficacy in vivo, and identify potential drug candidates that can be repositioned for use in humans.