Mesenchymal stem cell (MSC)-derived exosomes have emerged as an attractive cell-free tool in tissue engineering and regenerative medicine. The current study aimed to examine the anti-inflammatory, pro-angiogenic, and wound-repair effects of both exosomes and selenium-stimulated exosomes, and check whether the latter had superior wound healing capacity over others. The cellular and molecular network of exosomes, as a paracrine signal, was extensively studied by performing miRNA arrays to explore the key mediators of exosomes in wound healing. Selenium is known to play a critical role in enhancing the proliferation, multi-potency, and anti-inflammatory effects of MSCs. Selenium-stimulated exosomes showed significant effects in inhibiting inflammation and improving pro-angiogenesis in human umbilical vein endothelial cells. Cell growth and the migration of human dermal fibroblasts and wound regeneration were more enhanced in the selenium-stimulated exosome group than in the selenium and exosome groups, thereby further promoting the wound healing in vivo. Taken together, selenium was found to augment the therapeutic effects of adipose MSC-derived exosomes in tissue regeneration. We concluded that selenium may be considered a vital agent for wound healing in stem cell-based cell-free therapies.

The positive effects of mesenchymal stem cells (MSCs) are primarily activated through molecular secretions known as paracrine activity, which regulates the function of various cell types including immune cells. Accumulating evidence shows that exosomes of soluble factors released from MSCs are potential alternative agents for stem cell‐based therapy, although the exact underlying mechanism has not been elucidated. The purpose of this study was to evaluate the potential effects of exosomes produced by adipose‐derived MSCs and to examine the changes in anti‐inflammatory genes in concurrence with the polarization of M2 macrophages in cellular models ex vivo. Isolated exosomes were used to investigate the inflammatory modulation in pro‐inflammatory cytokine‐treated fibroblasts and THP‐1 cells. The anti‐inflammatory mRNA expression associated with M2 macrophages was significantly upregulated after exosome treatment in an interferon gamma and tumor necrosis factor alpha‐treated inflammatory environment. Furthermore, melatonin‐stimulated exosomes exerted superior anti‐inflammatory modulation via exosomal miRNAs miR‐34a, miR‐124, and miR‐135b, compared with exosomes. Our results indicate that melatonin‐stimulated exosomes originating from adipose‐derived MSCs are safe and efficient tools for regenerative medicine to treat inflammatory diseases.

June Seok HEO. Korean J Clin Lab Sci. 2024;56:1-9. https://doi.org/10.15324/kjcls.2024.56.1.1