Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing

Abstract Much of the therapeutic potential of mesenchymal stromal cells (MSCs) is underpinned by their secretome which varies significantly with source, donor and microenvironmental cues. Understanding these differences is essential to define the mechanisms of MSC-based tissue repair and optimise ce...

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Main Authors: Margeaux Hodgson-Garms, Matthew J. Moore, Mikaël M. Martino, Kilian Kelly, Jessica E. Frith
Format: Article
Language:English
Published: Nature Portfolio 2025-02-01
Series:npj Regenerative Medicine
Online Access:https://doi.org/10.1038/s41536-024-00382-y
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author Margeaux Hodgson-Garms
Matthew J. Moore
Mikaël M. Martino
Kilian Kelly
Jessica E. Frith
author_facet Margeaux Hodgson-Garms
Matthew J. Moore
Mikaël M. Martino
Kilian Kelly
Jessica E. Frith
author_sort Margeaux Hodgson-Garms
collection DOAJ
description Abstract Much of the therapeutic potential of mesenchymal stromal cells (MSCs) is underpinned by their secretome which varies significantly with source, donor and microenvironmental cues. Understanding these differences is essential to define the mechanisms of MSC-based tissue repair and optimise cell therapies. This study analysed the secretomes of bone-marrow (BM.MSCs), umbilical-cord (UC.MSCs), adipose-tissue (AT.MSCs) and clinical/commercial-grade induced pluripotent stem cell-derived MSCs (iMSCs), under resting and inflammatory licenced conditions. iMSCs recapitulated the inflammatory licensing process, validating their comparability to tissue-derived MSCs. Overall, resting secretomes were defined by extracellular matrix (ECM) and pro-regenerative proteins, while licensed secretomes were enriched in chemotactic and immunomodulatory proteins. iMSC and UC.MSC secretomes contained proteins indicating proliferative potential and telomere maintenance, whereas adult tissue-derived secretomes contained fibrotic and ECM-related proteins. The data and findings from this study will inform the optimum MSC source for particular applications and underpin further development of MSC therapies.
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spelling doaj-art-99cd0911d6eb44e9a04c02c24677ce772025-02-09T12:16:20ZengNature Portfolionpj Regenerative Medicine2057-39952025-02-0110111810.1038/s41536-024-00382-yProteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensingMargeaux Hodgson-Garms0Matthew J. Moore1Mikaël M. Martino2Kilian Kelly3Jessica E. Frith4Department of Materials Science and Engineering, Monash UniversityDepartment of Materials Science and Engineering, Monash UniversityAustralian Regenerative Medicine InstituteCynata TherapeuticsDepartment of Materials Science and Engineering, Monash UniversityAbstract Much of the therapeutic potential of mesenchymal stromal cells (MSCs) is underpinned by their secretome which varies significantly with source, donor and microenvironmental cues. Understanding these differences is essential to define the mechanisms of MSC-based tissue repair and optimise cell therapies. This study analysed the secretomes of bone-marrow (BM.MSCs), umbilical-cord (UC.MSCs), adipose-tissue (AT.MSCs) and clinical/commercial-grade induced pluripotent stem cell-derived MSCs (iMSCs), under resting and inflammatory licenced conditions. iMSCs recapitulated the inflammatory licensing process, validating their comparability to tissue-derived MSCs. Overall, resting secretomes were defined by extracellular matrix (ECM) and pro-regenerative proteins, while licensed secretomes were enriched in chemotactic and immunomodulatory proteins. iMSC and UC.MSC secretomes contained proteins indicating proliferative potential and telomere maintenance, whereas adult tissue-derived secretomes contained fibrotic and ECM-related proteins. The data and findings from this study will inform the optimum MSC source for particular applications and underpin further development of MSC therapies.https://doi.org/10.1038/s41536-024-00382-y
spellingShingle Margeaux Hodgson-Garms
Matthew J. Moore
Mikaël M. Martino
Kilian Kelly
Jessica E. Frith
Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing
npj Regenerative Medicine
title Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing
title_full Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing
title_fullStr Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing
title_full_unstemmed Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing
title_short Proteomic profiling of iPSC and tissue-derived MSC secretomes reveal a global signature of inflammatory licensing
title_sort proteomic profiling of ipsc and tissue derived msc secretomes reveal a global signature of inflammatory licensing
url https://doi.org/10.1038/s41536-024-00382-y
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