Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes

Abstract Mesenchymal stromal cells (MSCs) from both humans and horses, which represent a clinically relevant translation animal model for human cutaneous wound healing, were recently found to possess antimicrobial properties against planktonic bacteria, and in the case of equine MSCs, also against b...

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Autores principales:	Charlotte Marx, Sophia Gardner, Rebecca M. Harman, Bettina Wagner, Gerlinde R. Van de Walle
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	antimicrobial peptides biofilm cutaneous wounds keratinocytes mesenchymal stromal cells MRSA Medicine (General) R5-920 Cytology QH573-671
Acceso en línea:	https://doaj.org/article/e2cf83929ad54c3ca8999bd7724d961a
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spelling	oai:doaj.org-article:e2cf83929ad54c3ca8999bd7724d961a2021-12-03T12:11:46ZMesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes2157-65802157-656410.1002/sctm.21-0058https://doaj.org/article/e2cf83929ad54c3ca8999bd7724d961a2021-12-01T00:00:00Zhttps://doi.org/10.1002/sctm.21-0058https://doaj.org/toc/2157-6564https://doaj.org/toc/2157-6580Abstract Mesenchymal stromal cells (MSCs) from both humans and horses, which represent a clinically relevant translation animal model for human cutaneous wound healing, were recently found to possess antimicrobial properties against planktonic bacteria, and in the case of equine MSCs, also against biofilms. This, together with previous findings that human and equine MSCs promote angiogenesis and wound healing, makes these cells an attractive approach to treat infected cutaneous wounds in both species. The anti‐biofilm activities of equine MSC, via secretion of cysteine proteases, have only been demonstrated in vitro, thus lacking information about in vivo relevance. Moreover, the effects of the equine MSC secretome on resident skin cells have not yet been explored. The goals of this study were to (a) test the efficacy of the MSC secretome in a physiologically relevant ex vivo equine skin biofilm explant model and (b) explore the impact of the MSC secretome on the antimicrobial defense mechanisms of resident skin cells. Our salient findings were that secreted factors from equine MSCs significantly decreased viability of methicillin‐resistant Staphylococcus aureus bacteria in mature biofilms in this novel skin biofilm explant model. Moreover, we demonstrated that equine MSCs secrete CCL2 that increases the antimicrobial activity of equine keratinocytes by stimulating expression of antimicrobial peptides. Collectively, these data contribute to our understanding of the MSC secretome's antimicrobial properties, both directly by killing bacteria and indirectly by stimulating immune responses of surrounding resident skin cells, thus further supporting the value of MSC secretome‐based treatments for infected wounds.Charlotte MarxSophia GardnerRebecca M. HarmanBettina WagnerGerlinde R. Van de WalleWileyarticleantimicrobial peptidesbiofilmcutaneous woundskeratinocytesmesenchymal stromal cellsMRSAMedicine (General)R5-920CytologyQH573-671ENStem Cells Translational Medicine, Vol 10, Iss 12, Pp 1666-1679 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	antimicrobial peptides biofilm cutaneous wounds keratinocytes mesenchymal stromal cells MRSA Medicine (General) R5-920 Cytology QH573-671
spellingShingle	antimicrobial peptides biofilm cutaneous wounds keratinocytes mesenchymal stromal cells MRSA Medicine (General) R5-920 Cytology QH573-671 Charlotte Marx Sophia Gardner Rebecca M. Harman Bettina Wagner Gerlinde R. Van de Walle Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
description	Abstract Mesenchymal stromal cells (MSCs) from both humans and horses, which represent a clinically relevant translation animal model for human cutaneous wound healing, were recently found to possess antimicrobial properties against planktonic bacteria, and in the case of equine MSCs, also against biofilms. This, together with previous findings that human and equine MSCs promote angiogenesis and wound healing, makes these cells an attractive approach to treat infected cutaneous wounds in both species. The anti‐biofilm activities of equine MSC, via secretion of cysteine proteases, have only been demonstrated in vitro, thus lacking information about in vivo relevance. Moreover, the effects of the equine MSC secretome on resident skin cells have not yet been explored. The goals of this study were to (a) test the efficacy of the MSC secretome in a physiologically relevant ex vivo equine skin biofilm explant model and (b) explore the impact of the MSC secretome on the antimicrobial defense mechanisms of resident skin cells. Our salient findings were that secreted factors from equine MSCs significantly decreased viability of methicillin‐resistant Staphylococcus aureus bacteria in mature biofilms in this novel skin biofilm explant model. Moreover, we demonstrated that equine MSCs secrete CCL2 that increases the antimicrobial activity of equine keratinocytes by stimulating expression of antimicrobial peptides. Collectively, these data contribute to our understanding of the MSC secretome's antimicrobial properties, both directly by killing bacteria and indirectly by stimulating immune responses of surrounding resident skin cells, thus further supporting the value of MSC secretome‐based treatments for infected wounds.
format	article
author	Charlotte Marx Sophia Gardner Rebecca M. Harman Bettina Wagner Gerlinde R. Van de Walle
author_facet	Charlotte Marx Sophia Gardner Rebecca M. Harman Bettina Wagner Gerlinde R. Van de Walle
author_sort	Charlotte Marx
title	Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
title_short	Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
title_full	Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
title_fullStr	Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
title_full_unstemmed	Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
title_sort	mesenchymal stromal cell‐secreted ccl2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/e2cf83929ad54c3ca8999bd7724d961a
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_version_	1718373301919678464

Mesenchymal stromal cell‐secreted CCL2 promotes antibacterial defense mechanisms through increased antimicrobial peptide expression in keratinocytes

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