Hodgson-Garms Margeaux, Moore Matthew J, Martino Mikaël M, Kelly Kilian, Frith Jessica E
Department of Materials Science and Engineering, Monash University, Melbourne, VIC, Australia.
Cynata Therapeutics, Melbourne, VIC, Australia.
NPJ Regen Med. 2025 Feb 4;10(1):7. doi: 10.1038/s41536-024-00382-y.
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.
间充质基质细胞（MSCs）的许多治疗潜力都源于其分泌组，而分泌组会因来源、供体和微环境线索的不同而有显著差异。了解这些差异对于明确基于MSCs的组织修复机制以及优化细胞疗法至关重要。本研究分析了在静息和炎症许可条件下，骨髓（BM.MSCs）、脐带（UC.MSCs）、脂肪组织（AT.MSCs）以及临床/商业级诱导多能干细胞衍生的MSCs（iMSCs）的分泌组。iMSCs重现了炎症许可过程，验证了其与组织来源MSCs的可比性。总体而言，静息分泌组由细胞外基质（ECM）和促再生蛋白定义，而许可分泌组富含趋化和免疫调节蛋白。iMSC和UC.MSC分泌组含有表明增殖潜力和端粒维持的蛋白，而成人组织来源的分泌组则含有纤维化和ECM相关蛋白。本研究的数据和发现将为特定应用提供最佳MSCs来源，并为MSCs疗法的进一步发展提供支持。
