Adipose Stem Cell-Derived Apoptotic Vesicles Attenuate Hypertrophic Scarring by Targeting the CDC20/WNT Signaling Pathway

Background: Apoptotic vesicles (ApoVs) derived from adipose stem cells (ASCs) have recently emerged as important mediators of tissue repair and are implicated in pathways relevant to hypertrophic scar (HS). Although ASCs exhibit potential in scar modulation, the therapeutic value of their apoptotic clearance products remains largely unexplored. Methods: In this study, we investigated the efficacy and mechanism of staurosporine (STS)-induced adipose stem cell derived apoptotic vesicles (ASCs-ApoVs) in mitigating HS. Western blot, RT-qPCR, and immunofluorescence were used to assess fibrotic markers including α-SMA, COL1A1, and COL3A1 and so on in hypertrophic scar derived fibroblasts (HS-fibroblasts). Results: ASCs-ApoVs significantly reduced profibrotic marker expression in HS-fibroblasts without short-term cytotoxicity. CDC20 down-regulation was identified as a critical target, through which ASCs-ApoVs suppressed Wnt/β-catenin signaling, as evidenced by the downregulation of β-catenin, c-MYC, Cyclin D1, and AXIN2. The efficacy of ASCs-ApoVs in hypertrophic scar regulation was also confirmed by the rabbit ear scar model. Furthermore, ASCs-ApoVs demonstrated notable structural and functional stability. Conclusions: In summary, our results established STS-induced ASCs-ApoVs as a potent multi-target strategy for hypertrophic scar regulation. Besides, the scalable production, functional stability, and favorable safety profile of ASCs-ApoVs underscore a strong promise for clinical translation.