PMC

Workflow of ASC‐sEV production, purification and characterization. Human ASCs were expanded in culture flasks and small EV‐enriched conditioned medium was collected. sEVs were purified via TFF and sucrose cushion ultracentrifugation. Purified sEVs were extensively characterized for their identity and content profiling. ASCs, adipose‐derived mesenchymal stem cells; EV; extracellular vesicles; sEV, small EV; TFF, tangential flow filtration.

Results of skin improvements 6 months after SVF injection.

Summary of this study. PDLLA enhances pNRF2/NRF2 expression in macrophages, which leads to increased M2 polarization and IL-10 expression in senescent macrophages and aged skin. This increase in IL-10 expression by macrophages leads to reduced senescence and increased proliferation and secretion of TGF-β and FGF2 in ASCs. The increase in TGF-β and FGF2 levels results in increased proliferation and synthesis of collagen and elastin fibers in fibroblasts. The PDLLA-modulated macrophage not only directly stimulated fibroblast activity, promoting proliferation and collagen synthesis, but also reduced the expression of NF-κB and MMP2/3/9. These effects ultimately led to skin rejuvenation in aged skin.

Effects of loaded ASC‐sEVs on human skin. (A) Experimental design to examine the effects of loaded EVs on human skin. For each participant, the left hand was treated with vehicle while the right hand was treated with loaded EVs, once a day for 8 weeks and skin was examined every other week by Gpskin, API‐100 and Antera 3D devices. (B) Representative micrographs from one volunteer showing differences in pigmentation, redness, texture, pore, and melanin level from skin treated with either vehicle or loaded sEVs at baseline and after 8 weeks of treatment. (C) Quantification of barrier score, moisture, transepidermal water loss, stratum corneum hydration, elasticity, mean pore volume, and melanin level from skin treated with either vehicle or loaded sEVs at baseline and after 8 weeks of treatment (n = 3 participants). *p < 0.05, Student's t‐test. ASCs, adipose‐derived mesenchymal stem cells; sEV, small EV.