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A Sheet of Exosomes Derived from Adipose Stem Cells Modulates Oral Mucosal Wound Healing
Dany Y. Matar
*1, Chung-Jan Kang
2, Adriana C. Panayi
3, Dennis P. Orgill
3, Huang-Kai Kao
21Johns Hopkins University School of Medicine, Baltimore, MD; 2Chang Gung Memorial Hospital, Taoyuan, Taiwan; 3Brigham and Women's Hospital, Harvard Medical School, Boston, MA
Introduction: Oral mucosal wound healing remains poorly understood, with limited treatment options. This study evaluates whether an exosome sheet derived from adipose-derived stem cells (ADSCs) can enhance intraoral wound healing in a rat model.
Methods: Sixteen rats received 6mm full-thickness excisional palatal mucosal wounds. Eight were treated with an ADSC exosome sheet (Tisseel and rat ADSC-derived exosomes) under an occlusive dressing; eight received the dressing alone. Wound closure was tracked on days 0, 2, 4, 7, and 10. On day 10, tissues were harvested (n=8/group) for immunohistochemical analysis. In vitro, fibroblast migration was assessed after treatment with 0, 4.5e11, 9e11, or 18e11 exosomes/mL (n=4/group).
Results: ADSC-exo significantly accelerated wound closure (35±9% vs. 18±5% of initial area;
p=0.002) and fibroblast migration at 24 hr (62.2±4% vs. 29.7±3%;
p<0.0001). Treated wounds showed enhanced re-epithelialization (87±14% vs. 21±6%;
p<0.0001), proliferation (34±12 vs. 18±7 Ki67+/HPF;
p=0.004), and neovascularization (28±9 vs. 11±5 CD31+/HPF;
p=0.0002), along with reduced inflammation (4±1 vs. 13±9 CD68+/HPF;
p<0.0001) and greater M2 macrophage presence (9.2±2 vs. 4.2±3 CD163+/HPF;
p=0.0008). ADSC-exo upregulated 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), and downregulated 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).
Conclusions: ADSC-exo significantly enhances intraoral wound healing, potentially via activation of the TGF-β/Smad pathway. This is the first study to demonstrate the therapeutic potential of an ADSC exosome sheet in mucosal repair, supporting further translational investigation.
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