Protecting and rejuvenating ageing skin by regulating endogenous hyaluronan metabolism using adipose-derived stem cell-secreted siRNAs.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Background Loss of moisture is the primary cause of skin ageing and dysfunction. The skin's hydration largely depends on hyaluronan (HA) and its ability to retain water. Ultraviolet (UV) irradiation, which accounts for 80% of skin ageing (commonly referred to as photoaging), gradually disrupts the balance of HA metabolism, leading to a reduction in HA levels, dehydration, and, ultimately, the formation of wrinkles. Methods In this study, we develop an RNAi-based strategy to treat aged skin by modulating endogenous HA metabolism. Hyaluronidase 2 (HYAL2), an enzyme responsible for HA degradation, is selected as the therapeutic target, given its significant upregulation in photoaged skin. To deliver the siRNA targeting HYAL2 to the skin, human adipose-derived stem cells (ADSCs) are engineered to stably express and secrete HYAL2-targeting siRNAs (ADSC/siR H ) via small extracellular vesicles (sEVs). Results In vitro experiments demonstrate that ADSC-delivered siRNAs are successfully internalised by recipient cells, where they restore UV-induced HA reduction by inhibiting HYAL2 expression. In vivo experiments revealed that subcutaneous implantation of engineered ADSCs prior to UV exposure significantly protects mouse skin from accelerated HA degradation, helping to retain water content and prevent UV-induced dryness. Furthermore, the application of engineered ADSCs to aged mouse ski

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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