Alterations in Immunomodulatory Potential of ADSCs Undergoing Osteogenic Differentiation in the Context of Future Therapeutic Applications

Background: Adipose-derived mesenchymal stem/stromal cells (ADSCs) are gaining recognition in regenerative medicine for their potential for adipogenic, osteogenic, and chondrogenic differentiation, as well as their immunomodulatory properties. However, ADSC-based therapies focus either on differentiation for tissue replacement or on counteracting unrestrained inflammation to prevent tissue destruction and initiate regeneration. Here, we aim to examine the immunomodulatory potential of osteogenically differentiated ADSCs by analyzing their proteomic profile. Methods: Using LC-MS/MS, we generated the proteomic profiles of differentiated and undifferentiated ADSCs and compared them with the Reactome database. Transcriptomic analysis was also performed and compared with the proteomic profile. Results: Comparison of the proteomic (499 up-regulated; 355 down-regulated) and transcriptomic (212 up-regulated; 232 down-regulated) profiles showed 60.1% concordance—both proteins and transcripts showed the same trend. Significantly upregulated proteins in differentiating ADSCs (−log10 p > 5 and >10) were grouped into four categories: propensity for osteogenic differentiation; immunomodulation/immune/inflammatory response; cell senescence; and cell cycle regulation. Among those proteins, thirteen were reported to play roles in processes such as immunomodulation, inflammatory signaling, or transplant rejection. Conclusions: We observed that differentiating ADSCs might still exert immunomodulatory effects, which could be used in the treatment of, e.g., bone defects.