Fig. 2.

Components, mode of action, and indication of paracrine factor-based therapies. The cell secretome consists of multiple paracrine factors that can be categorized into different biological classes. The best investigated components are proteins, lipids, and exosomes, which have been shown to exhibit in vitro and in vivo biological activity. Due to the complexity of paracrine factors present in the cell secretome, it is likely that other factors exert biological activity. Paracrine factors derived from apoptotic PBMCs have been shown to induce angiogenesis and vasodilation, exert antimicrobial activity, enhance re-epithelialization, inhibit platelet coagulation, induce M1–M2 polarization, augment the release of neurotropic factors, exhibit cytoprotective capacities due to the up-regulation of anti-apoptotic proteins, and act in an immunomodulatory manner. Based on these biological effects, the PBMC secretome has been successfully tested in animal models to treat acute myocardial infarction, chronic heart failure, myocarditis, skin ulcer, stroke, and spinal cord injury