The therapeutic effect of topical injection of adipose stem cell-derived extracellular vesicles at different time intervals on wound healing in mice

Abstract

Adipose-derived stem cell extracellular vesicles (ADEVs) have emerged as a promising biotherapeutic agent, demonstrating efficacy in treating various skin diseases, including wound healing, through local injection. The concentration of ADEVs and the optimal injection interval are critical factors influencing their therapeutic outcomes. However, the optimal dosage and injection intervals for ADEVs in wound healing remain to be elucidated. In this study, we harvested ADEVs from adipose-derived stem cells (ADSCs) of mice and used in vivo imaging to track the local concentration of these vesicles following topical injection. We also evaluated the therapeutic effects of ADEVs on wound healing at different time intervals (4 days, 8 days, and 16 days). Our results indicated that ADEVs injected at concentration over 200 μg/mL persist in skin for more than 7 days. Notably, injection intervals of 4 days and 8 days significantly enhanced wound healing, whereas the 16-day interval did not show such benefits. Additionally, the skin scar tissues in the 4-day and 8-day groups exhibited normal skin structures and appendages, including hair follicles and sebaceous glands. In conclusion, the injection concentration and time intervals influence the outcomes of therapeutic effects of ADEVs under equal total dosages. ADEVs injected at concentration over 200 μg/mL harm the wound healing process with excessive accumulation and unexpected inflammation. Topical injection of ADEVs at a concentration of 50 μg/mL every 4 days or 100 μg/mL every 8 days promote wound healing and skin structure remodeling by regulating angiogenesis-related genes expression.