Identification of drugs that enhance skin repair using dermal stem cell-based screens [Mouse]. Mus musculus

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. Overall design: We obtained three independent isolates of SKPs from 9 month old CD57/Bl6 mice which were either uninjured and treated with vehicle, injured and treated with vehicle, trimebutine maleate, or alprostadil. RNA samples deriving from these cells were analyzed on the Affymetrix GeneChip Mouse Gene 2.0 ST Array.