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

IF 6.5 1区医学 Q1 CELL & TISSUE ENGINEERING npj Regenerative Medicine Pub Date : 2025-02-04 DOI:10.1038/s41536-024-00382-y

Margeaux Hodgson-Garms, Matthew J Moore, Mikaël M Martino, Kilian Kelly, Jessica E Frith

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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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iPSC和组织来源的MSC分泌组的蛋白质组学分析揭示了炎症许可的全球特征。

间充质基质细胞（MSCs）的治疗潜力很大程度上取决于它们的分泌组，分泌组随来源、供体和微环境因素而显著不同。了解这些差异对于定义基于msc的组织修复机制和优化细胞治疗至关重要。本研究分析了静息和炎症条件下骨髓（BM.MSCs）、脐带（UC.MSCs）、脂肪组织（AT.MSCs）和临床/商业级诱导多能干细胞来源的MSCs （iMSCs）的分泌组。iMSCs重现了炎症许可过程，验证了它们与组织来源的MSCs的可比性。总的来说，静息分泌组由细胞外基质（ECM）和促再生蛋白定义，而许可分泌组则富含趋化蛋白和免疫调节蛋白。iMSC和UC。间充质干细胞分泌组含有指示增殖潜能和端粒维持的蛋白质，而成体组织来源的分泌组含有纤维化和ecm相关蛋白质。这项研究的数据和发现将为特定应用的最佳MSC来源提供信息，并为MSC疗法的进一步发展奠定基础。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

npj Regenerative Medicine Engineering-Biomedical Engineering

CiteScore

10.00

自引率

1.40%

发文量

审稿时长

12 weeks

期刊介绍： Regenerative Medicine, an innovative online-only journal, aims to advance research in the field of repairing and regenerating damaged tissues and organs within the human body. As a part of the prestigious Nature Partner Journals series and in partnership with ARMI, this high-quality, open access journal serves as a platform for scientists to explore effective therapies that harness the body's natural regenerative capabilities. With a focus on understanding the fundamental mechanisms of tissue damage and regeneration, npj Regenerative Medicine actively encourages studies that bridge the gap between basic research and clinical tissue repair strategies.