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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 cellderived

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