Exosomes from human adipose-derived mesenchymal stem cells inhibit production of extracellular matrix in keloid fibroblasts via downregulating transforming growth factor-β2 and Notch-1 expression

Keloids are an excessive tissue response to dermal damage, characterized by uncontrolled growth and a high recurrence rate after various treatments. Abnormalities with the extracellular matrix (ECM) are one of the most important contributing factors to the formation of keloids. Although exosomes from human adipose-derived mesenchymal stem cells (adMSC-Exos) have been shown to promote repair and regeneration in wounds, they have seldom been studied for the treatment of keloids. In this study, we aimed to investigate the effects of adMSC-Exos on ECM remodeling in keloids using both in vitro and ex vivo models. The results showed that adMSC-Exos inhibited gene and protein expression of collagen I (COL-1), collagen III (COL-3), fibronectin (FN), and alpha-smooth muscle actin (alpha-SMA) in keloid fibroblasts (KFs). Furthermore, using an ex vivo tissue explant model, we found that adMSC-Exos significantly suppressed COL production and disrupted the microvessel stucture. We also demonstrated that adMSC-Exos inhibited the protein expression of Smad3 and Notch-1, and the expression of transforming growth factor beta 2 (TGF-beta 2) in KFs, and promoted the expression of TGF-beta 3. These findings largely explain the mechanisms underlying the inhibition of ECM production in keloids by adMSC-Exos. In conclusion, our results revealed that adMSC-Exos effectively inhibited the production of ECM in keloids, which provides a new potential alternative for the systemic treatment of keloids. [GRAPHICS]

Automated summary

This study investigated the effects of exosomes from human adipose-derived mesenchymal stem cells (adMSC-Exos) on extracellular matrix (ECM) remodeling in keloids. The results showed that adMSC-Exos inhibited the expression of collagen and fibronectin, disrupted collagen production and microvessel structure, and had an impact on the protein expression of certain factors involved in ECM production. These findings provide a new potential alternative for the treatment of keloids by targeting ECM production.