Adipose-derived exosomes as a preventative strategy against complications in hyaluronic acid filler applications: A comprehensive in vivo analysis

초록

Background: The aim of this study was to investigate the impact of exosomes derived from adipose-derived stem cells (ASCs) on complications arising from hyaluronic acid (HA) filler injections. Methods: An HA hydrogel blended with adipose stem cell-derived exosomes was prepared and administered to the inguinal fat pads of 16 C57BL/6J mice. The control group received only HA filler (HA group), and the study group was treated with a combination of HA filler and exosomes (exoHA group). Biopsy was performed 1 week and 1, 2, 3, and 6 months after the injections. The effects were assessed using hematoxylin and eosin and Masson's trichrome staining for histological examination, immunohistochemistry for collagen type I and Vascular Endothelial Growth Factor (VEGF), RNA sequencing, and quantitative real-time polymerase chain reaction (PCR) (Il6, Ifng, Hif1a, Acta2, Col1a1). Results: RNA sequencing revealed significant downregulation of the hypoxia (false discovery rate [FDR] q = 0.007), inflammatory response (FDR q = 0.009), TNF alpha signaling via NF kappa B (FDR q = 0.007), and IL6 JAK-STAT signaling (FDR q = 0.009) gene sets in the exoHA group. Quantitative PCR demonstrated a decrease in expression of proinflammatory cytokines (Il6, P < 0.05; Hif1a, P < 0.05) and fibrosis markers (Acta2, P < 0.05; Col1a1, P < 0.05) within the exoHA group, indicating reduced inflammation and fibrosis. Compared to the exoHA group, the HA group exhibited a thicker and more irregular capsules surrounding the HA filler after 6 months. Conclusion: The addition of ASC-derived exosomes to HA fillers significantly reduces inflammation and accelerates collagen capsule maturation, indicating a promising strategy to mitigate the formation of HA filler-related nodules. (c) 2024 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.

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