MSC secretomes as a cell-free therapeutic platform: Molecular heterogeneity, disease-specific bioactivity, delivery strategies, and regulatory translation across six major disease areas.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

The mesenchymal stromal/stem cell (MSC) secretome is emerging as a cell-free pharmacological agent with multitarget activity in regenerative and inflammatory diseases. Rather than durable engraftment or differentiation, most therapeutic effects of MSC-based therapies are mediated by a complex mixture of soluble factors and extracellular vesicles (EVs) that can, in principle, be formulated as standardized biological drugs. This review appraises current evidence on MSC secretome composition, mechanisms of action, and pharmacological profile, emphasizing its potential as a scalable off-the-shelf platform. We first characterize the source-dependent architecture of the MSC secretome derived from bone marrow, adipose tissue, and umbilical cord, identifying a conserved core of 894 shared proteins alongside tissue-specific signatures that determine differential bioactivity. Pharmacologically active components are classified by mechanism, encompassing anti-inflammatory, pro-angiogenic, neuroprotective, antifibrotic, and regenerative mediators. We then critically examine preclinical evidence for secretome- and EV-based interventions across cardiovascular, neurological, ocular, inflammatory, musculoskeletal, and dermatological diseases, comparing mechanistic profiles, delivery routes, and potential advantages over current standard-of-care therapies. Finally, we address key translational c

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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