Niu Qiang, Guo Yan, Zhang Zhou, Gong Jing, Liu Fei, Kong Yu
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, National Clinical Research Center for Oral Diseases, Shaanxi Clinical Research Center for Oral Diseases, Department of Oral and Maxillofacial Surgery, School of Stomatology, The Fourth Military Medical University, No. 169 Changle West Road, Xi'an, 710032, Shaanxi, China.
Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University, No. 98 XiWu Road, Xi'an, 710004, Shaanxi, China; Department of Emergency Room, College of Stomatology, Xi'an Jiaotong University, No. 98 XiWu Road, Xi'an, 710004, Shaanxi, China.
Biochem Biophys Res Commun. 2025 Aug 30;776:152223. doi: 10.1016/j.bbrc.2025.152223. Epub 2025 Jun 17.
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.
脂肪来源干细胞外泌体（ADEVs）已成为一种有前景的生物治疗剂，通过局部注射在治疗包括伤口愈合在内的各种皮肤病方面显示出疗效。ADEVs的浓度和最佳注射间隔是影响其治疗效果的关键因素。然而，ADEVs在伤口愈合中的最佳剂量和注射间隔仍有待阐明。在本研究中，我们从小鼠脂肪来源干细胞（ADSCs）中收获ADEVs，并使用体内成像技术跟踪局部注射后这些囊泡的局部浓度。我们还评估了ADEVs在不同时间间隔（4天、8天和16天）对伤口愈合的治疗效果。我们的结果表明，浓度超过200μg/mL注射的ADEVs在皮肤中持续存在超过7天。值得注意的是，4天和8天的注射间隔显著促进了伤口愈合，而16天的间隔则没有显示出这种效果。此外，4天和8天组的皮肤瘢痕组织表现出正常的皮肤结构和附属器，包括毛囊和皮脂腺。总之，在总剂量相等的情况下，注射浓度和时间间隔会影响ADEVs的治疗效果。浓度超过200μg/mL注射的ADEVs会因过度积累和意外炎症而损害伤口愈合过程。每4天以50μg/mL的浓度或每8天以100μg/mL的浓度局部注射ADEVs，通过调节血管生成相关基因的表达促进伤口愈合和皮肤结构重塑。
