An Adipose-Derived Stem Cell Exosome Sheet Promotes Oral Mucosal Wound Healing.

IF 5.8 3区医学 Q1 DERMATOLOGY

Advances in wound care Pub Date : 2025-05-07 DOI:10.1089/wound.2024.0216

Dany Y Matar, Chung-Jan Kang, Adriana C Panayi, Dennis P Orgill, Huang-Kai Kao

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引用次数: 0

Abstract

Objective: Oral mucosal wound healing is not completely understood, and effective therapies are lacking. This study explores the potential of an adipose-derived stem cell (ADSC) exosome sheet in enhancing intraoral wound healing in rats. Approach: An ADSC exosome sheet derived from Tisseel and rat adipose tissue (ADSC-exo) was applied to 16 rats with 6 mm full-thickness mucosal hard palate wounds. Eight wounds received ADSC-exo with a superficial occlusive dressing (ADSC-exo group), and eight received only an occlusive dressing (control group). Wound closure was monitored on days 0, 2, 4, 7, and 10, with dressings changed every 2 days. On day 10, rats were sacrificed, and wounds (n = 8 per group) were collected for immunohistochemical analysis. In vitro, four ADSC-exosome concentrations (0, 4.5 × 10¹¹, 9 × 10¹¹, and 18 × 10¹¹ exosomes/mL; n = 4 per group) were applied to rat oral mucosal fibroblasts to assess migration speed. Results: ADSC-exo accelerated wound closure (18% ± 5% vs. 35% ± 9% of initial wound area; p = 0.002) and fibroblast migration (for 18 × 10¹¹ exosomes/mL at 24 h: 29.7% ± 3% vs. 62.2% ± 4% of initial gap area; p < 0.0001) compared with the control. ADSC-exo promoted reepithelialization (87% ± 14% vs. 21% ± 6%; p < 0.0001), proliferation (34 ± 12 vs. 18 ± 7 Ki67+/high-power field [HPF]; p = 0.004), and neovascularization (28 ± 9 vs. 11 ± 5 CD31+/HPF; p = 0.0002) while reducing inflammation (4 ± 1 vs. 13 ± 9 CD68+/HPF; p < 0.0001) and increasing M2 macrophages (9.2 ± 2 vs. 4.2 ± 3 CD163+/HPF; p = 0.0008). ADSC-exo increased Transforming Growth Factor beta 1 (TGF-β1) (1.3 ± 0.3 vs. 0.9 ± 0.2; p = 0.006), Smad3 (0.9 ± 0.02 vs. 0.7 ± 0.1; p = 0.006), and collagen I (1.5 ± 0.9 vs. 0.5 ± 0.3; p = 0.005) while downregulating caspase-3 (0.7 ± 0.3 vs. 1.1 ± 0.2; p = 0.003) and Bax (0.9 ± 0.2 vs. 1.4 ± 0.1; p < 0.0001). Innovation: This is the first study to demonstrate the pro-wound healing effects of an ADSC exosome sheet on intraoral wounds. This paves the way for future research and clinical applications of ADSC exosomes in mucosal wound healing. Conclusions: Application of an ADSC-exo to rat mucosal wounds significantly improved wound healing. Mechanistically, these effects may be linked to upregulated activity of the TGF-β/Smad pathway.

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脂肪来源的干细胞外泌体片促进口腔黏膜伤口愈合。

目的：口腔黏膜创面愈合尚不完全清楚，缺乏有效的治疗方法。本研究探讨了脂肪源性干细胞（ADSC）外泌体膜在促进大鼠口腔内伤口愈合中的潜力。方法：将取自Tisseel和大鼠脂肪组织的ADSC外泌体片（ADSC-exo）应用于16只大鼠6 mm全层粘膜硬腭创面。8个创面采用ADSC-exo联合浅表闭塞敷料（ADSC-exo组），8个创面仅采用闭塞敷料（对照组）。在第0、2、4、7和10天监测伤口闭合情况，每2天更换一次敷料。第10天处死大鼠，收集创面（每组8只）进行免疫组织化学分析。体外，4种adsc外泌体浓度(0、4.5 × 1011、9 × 1011和18 × 1011外泌体/mL；每组N = 4)应用于大鼠口腔黏膜成纤维细胞，评估其迁移速度。结果：ADSC-exo加速创面愈合（18%±5% vs. 35%±9%）；p = 0.002)和成纤维细胞迁移(18 × 1011外泌体/mL， 24 h：初始间隙面积的29.7%±3% vs. 62.2%±4%；P < 0.0001)。ADSC-exo促进再上皮化(87%±14% vs. 21%±6%；p < 0.0001)，增殖(34±12比18±7 Ki67+/高倍场[HPF]；p = 0.004)，新生血管(28±9 vs 11±5 CD31+/HPF；p = 0.0002)，同时减少炎症(CD68+/HPF 4±1比13±9；p < 0.0001)， M2巨噬细胞增多(CD163+/HPF为9.2±2比4.2±3；P = 0.0008)。ADSC-exo增加转化生长因子β1 (TGF-β1)(1.3±0.3 vs. 0.9±0.2；p = 0.006), Smad3(0.9±0.02∶0.7±0.1；p = 0.006),胶原蛋白I(1.5±0.9和0.5±0.3;P = 0.005)，而下调caspase-3(0.7±0.3∶1.1±0.2；p = 0.003)和Bax(0.9±0.2 vs. 1.4±0.1；P < 0.0001)。创新：这是首次证明ADSC外泌体片对口腔内伤口的促伤口愈合作用的研究。这为未来ADSC外泌体在粘膜创面愈合中的研究和临床应用铺平了道路。结论：ADSC-exo应用于大鼠粘膜创面可显著改善创面愈合。从机制上讲，这些作用可能与TGF-β/Smad通路活性上调有关。

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来源期刊

Advances in wound care Medicine-Emergency Medicine

CiteScore

12.10

自引率

4.10%

发文量

期刊介绍： Advances in Wound Care rapidly shares research from bench to bedside, with wound care applications for burns, major trauma, blast injuries, surgery, and diabetic ulcers. The Journal provides a critical, peer-reviewed forum for the field of tissue injury and repair, with an emphasis on acute and chronic wounds. Advances in Wound Care explores novel research approaches and practices to deliver the latest scientific discoveries and developments. Advances in Wound Care coverage includes: Skin bioengineering, Skin and tissue regeneration, Acute, chronic, and complex wounds, Dressings, Anti-scar strategies, Inflammation, Burns and healing, Biofilm, Oxygen and angiogenesis, Critical limb ischemia, Military wound care, New devices and technologies.