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Accession IconGSE73328

Identification of drugs that enhance skin repair using dermal stem cell-based screens [Rat]

Organism Icon Rattus norvegicus
Sample Icon 12 Downloadable Samples
Technology Badge Icon Affymetrix Rat Gene 2.0 ST Array (ragene20st), Affymetrix Mouse Gene 2.0 ST Array (mogene20st)

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Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on SKPs (skin-derived precursors) a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance the self-renewal of human and rodent SKPs. We identified and validated 5 such compounds, and showed that two of them, alprostadil and trimebutine maleate, enhanced the repair of full thickness skin wounds in middle-aged mice. Moreover, SKPs isolated from drug-treated skin displayed long-term increases in self-renewal when cultured in basal growth medium without drugs. Both alprostadil and trimebutine maleate likely mediated increases in SKPs self-renewal by moderate hyperactivation of the MEK-ERK pathway. These findings identify candidates for potential clinical use in human skin repair, and provide support for the idea that pharmacological activation of endogenous tissue precursors represents a viable therapeutic strategy.
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