Research Summary:
The skin is a vital organ, serving as the body’s largest barrier, but its function declines with aging. As a result, research into effective regeneration treatments must continue to advance. Stem cell transplantation, a cell-based therapy, has become a popular treatment for skin aging, although it comes with drawbacks such as host immune reactions. To address this, stem cell-derived cell-free therapies have emerged as an alternative, backed by promising preclinical findings. The key components in cell-free therapy from stem cells are stem cell secretomes and extracellular vesicles (EVs). However, comprehensive reviews on the mechanisms of such treatments for skin aging remain limited.
Purpose: This review discusses the potential mechanisms of stem cell-derived cell-free therapy in preventing skin aging by identifying specific molecular targets suitable for these interventions.
Methods: A search was conducted, identifying 27 relevant in vitro studies on stem cell-derived cell-free therapy interventions in skin aging model cells, without restricting publication years, using PubMed, Scopus, and Google Scholar.
Results: Stem cell-derived cell-free therapy can prevent skin aging through various mechanisms, including: (1) involvement of multiple regenerative pathways (NF-kB, AP-1, MAPK, P-AKT, NRF2, SIRT-1); (2) oxidative stress regulation by reducing oxidants (HO-1, NQO1) and enhancing antioxidants (SOD1, CAT, GP, FRAP); (3) preventing ECM degradation by increasing elastin, collagen, HA, TIMP, and reducing MMP; (4) regulating cell activity by reducing cell senescence (SA-β-gal), apoptosis, and cell cycle arrest (P53, P12, P16), and enhancing autophagy, cell migration, and cell proliferation (Ki67); and (5) regulating the inflammatory pathway by reducing IL-6, IL-1, TNF-⍺, and increasing TGF-β. Several clinical trials have also revealed improvements in wrinkles, elasticity, hydration, pores, and pigmentation.
Conclusion: Stem cell-derived cell-free therapy is a promising novel treatment for skin aging by rejuvenating cells through various molecular mechanisms.
Keywords: cell-free therapy, extracellular vesicles, secretome, skin aging, stem cell.
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