Translational pathways for MSC secretome therapies: from bioprocessing to delivery

Mesenchymal stromal cells (MSCs) are multipotent, fibroblast-like cells known for their paracrine activity rather than long-term engraftment. Their secretome-the ensemble of soluble factors and extracellular vesicles released by these cells-is emerging as a designable, off-the-shelf biotherapeutic. Advances in scalable bioprocessing, closed downstream processing, and smart delivery enable good manufacturing practice-ready translation. This review outlines a product-focused road map linking cell sourcing, preconditioning, and bioreactor expansion with downstream processing steps. We highlight bottlenecks, including heterogeneity, stability, dose definition, and validated potency assays, and address regulatory implications for classification, comparability, and release. By reframing the MSC secretome as a manufactured product rather than a biological extract, we propose strategies to speed clinical readiness and establish it as a reproducible next-generation biotherapeutic.