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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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Autores principales: Naska, Sibel, Yuzwa, Scott A., Johnston, Adam P.W., Paul, Smitha, Smith, Kristen M., Paris, Maryline, Sefton, Michael V., Datti, Alessandro, Miller, Freda D., Kaplan, David R.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719140/
https://www.ncbi.nlm.nih.gov/pubmed/26724904
http://dx.doi.org/10.1016/j.stemcr.2015.12.002
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author Naska, Sibel
Yuzwa, Scott A.
Johnston, Adam P.W.
Paul, Smitha
Smith, Kristen M.
Paris, Maryline
Sefton, Michael V.
Datti, Alessandro
Miller, Freda D.
Kaplan, David R.
author_facet Naska, Sibel
Yuzwa, Scott A.
Johnston, Adam P.W.
Paul, Smitha
Smith, Kristen M.
Paris, Maryline
Sefton, Michael V.
Datti, Alessandro
Miller, Freda D.
Kaplan, David R.
author_sort Naska, Sibel
collection PubMed
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.
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spelling pubmed-47191402016-02-22 Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair Naska, Sibel Yuzwa, Scott A. Johnston, Adam P.W. Paul, Smitha Smith, Kristen M. Paris, Maryline Sefton, Michael V. Datti, Alessandro Miller, Freda D. Kaplan, David R. Stem Cell Reports Article 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. Elsevier 2015-12-24 /pmc/articles/PMC4719140/ /pubmed/26724904 http://dx.doi.org/10.1016/j.stemcr.2015.12.002 Text en © 2016 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Naska, Sibel
Yuzwa, Scott A.
Johnston, Adam P.W.
Paul, Smitha
Smith, Kristen M.
Paris, Maryline
Sefton, Michael V.
Datti, Alessandro
Miller, Freda D.
Kaplan, David R.
Identification of Drugs that Regulate Dermal Stem Cells and Enhance Skin Repair
title 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_short 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
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4719140/
https://www.ncbi.nlm.nih.gov/pubmed/26724904
http://dx.doi.org/10.1016/j.stemcr.2015.12.002
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