The role of the adipose-derived Stromal Vascular Fraction (SVF) secretome as an immunomodulator in the treatment of chronic inflammatory diseases through NF-κB and macrophage reprogramming.

Inflammatory responses trigger tissue damage through sustained activation of M1 macrophages and the NF-κB pathway. This review investigates the mechanism of action of the secretome derived from freshly isolated heterogeneous Stromal Vascular Fraction (SVF), distinct from culture-expanded stem cell conditioned media, in modulating the inflammatory response. This review summarizes the current literature on biochemical mechanisms that inhibit the NF-κB pathway and modulate the M1/M2 macrophage balance. SVF secretome components are proposed to modulate IKK complex phosphorylation and support the stabilization of IκBα, potentially hindering the nuclear translocation of p65/p50. At the same time, these components may encourage a metabolic shift to oxidative phosphorylation that supports M2-like polarization via the STAT6/PPAR-γ pathway. The SVF secretome is a potent immunomodulator that shifts microenvironments from destructive to regenerative. Recommendations: Further investigation should establish standardised GMP isolation methods and evaluate biochemical variability based on donor characteristics.