Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair
Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on skin-derived precursors (SKPs), a dermal precursor cell population. Libraries of compounds already used in humans were screened for their ability to enhance...
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Series: | Stem Cell Reports |
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doaj-4cd59b2569bd494892c8e39f93f2704b2020-11-24T22:41:56ZengElsevierStem Cell Reports2213-67112016-01-0161748410.1016/j.stemcr.2015.12.002Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin RepairSibel Naska0Scott A. Yuzwa1Adam P.W. Johnston2Smitha Paul3Kristen M. Smith4Maryline Paris5Michael V. Sefton6Alessandro Datti7Freda D. Miller8David R. Kaplan9Program in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaInstitute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON M5G 1X5, CanadaS.M.A.R.T. Laboratory for High-Throughput Screening Programs, Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, ON M5G 1X5, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaProgram in Neurosciences and Mental Health, Hospital for Sick Children, Toronto, ON M5G 0A4, CanadaHere, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on skin-derived precursors (SKPs), 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 five 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 SKP 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.http://www.sciencedirect.com/science/article/pii/S2213671115003677 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Sibel Naska Scott A. Yuzwa Adam P.W. Johnston Smitha Paul Kristen M. Smith Maryline Paris Michael V. Sefton Alessandro Datti Freda D. Miller David R. Kaplan |
spellingShingle |
Sibel Naska Scott A. Yuzwa Adam P.W. Johnston Smitha Paul Kristen M. Smith Maryline Paris Michael V. Sefton Alessandro Datti Freda D. Miller David R. Kaplan Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair Stem Cell Reports |
author_facet |
Sibel Naska Scott A. Yuzwa Adam P.W. Johnston Smitha Paul Kristen M. Smith Maryline Paris Michael V. Sefton Alessandro Datti Freda D. Miller David R. Kaplan |
author_sort |
Sibel Naska |
title |
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair |
title_short |
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair |
title_full |
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair |
title_fullStr |
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair |
title_full_unstemmed |
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair |
title_sort |
identification of drugs that regulate dermal stem cells and enhance skin repair |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2016-01-01 |
description |
Here, we asked whether we could identify pharmacological agents that enhance endogenous stem cell function to promote skin repair, focusing on skin-derived precursors (SKPs), 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 five 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 SKP 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. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671115003677 |
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