The Adipose-derived Stem Cell Secretome: Composition, Fibroblast Modulation, and Clinical Translation

Adipose-derived stem cells (ADSCs) have emerged as a key component in regenerative medicine due to their accessibility, immunomodulatory properties, and potent paracrine effects.Increasing evidence indicates that the therapeutic efficacy of ADSCs is largely mediated through their secretome, a complex ensemble of soluble growth factors, cytokines, chemokines, extracellular vesicles (EVs), and matrix-modulating enzymes.These secreted factors modulate crucial cellular processes including fibroblast proliferation, migration, extracellular matrix remodeling, and angiogenesis, making the ADSC secretome particularly effective in wound healing and dermal regeneration.Recent studies have demonstrated that the molecular composition of the secretome is dynamically influenced by environmental cues such as hypoxia and inflammatory stimuli, which can significantly enhance its regenerative potential.Notably, factors such as hepatocyte growth factor, vascular endothelial growth factor, interleukin-6, monocyte chemoattractant protein-1, and macrophage migration inhibitory factor, as well as microRNAs like miR-21 and miR-210 within EVs, contribute to fibroblast activation and immune modulation.Despite promising preclinical results and increasing interest in cell-free therapies, challenges remain in standardizing secretome production, ensuring batch-to-batch consistency, optimizing delivery methods, and navigating regulatory classifications.This review provides a comprehensive synthesis of current knowledge surrounding the ADSC secretome, highlighting its molecular constituents, biological functions on dermal fibroblasts, strategies for functional enhancement, and key considerations for clinical translation.