Modulating adipose-derived stromal cells’ secretomes by culture conditions: effects on angiogenesis, collagen deposition, and immunomodulation

The secretome of adipose-derived stromal cells (ASC) presents a promising avenue for cell-free therapies due to their rich mixture of bioactive molecules. Different culture conditions can modulate the composition of this mixture, but how this affects the functional properties of the secretome remains to be investigated. This study investigated the in vitro effects of normoxia, cytokines, high glucose, hypoxia, and hypoxia + high glucose-derived ASC secretomes on angiogenesis (tube formation assay), collagen deposition (Picrosirius-Red staining), and immunomodulation (One-way Mixed Lymphocyte Reaction in combination with an antibody-mediated cell-dependent cytotoxicity assay). The data showed that normoxia and hypoxia-derived secretomes consistently exhibited potent proangiogenic effects in both human and rat models. These secretomes also demonstrated positive influences on collagen deposition and immunomodulation. Interestingly, the human ASC hypoxia + high glucose-derived secretome emerged as a stimulator of collagen deposition and modulator of the immune system. Conversely, cytokines and high glucose-derived secretomes have shown less strong effects in almost all functional parameters. In conclusion, our findings indicate that modulating culturing conditions results in secretomes with different functional properties and emphasizes the multifaceted role of ASC secretomes in regenerative processes.