Department of Plastic and Aesthetic Surgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, 150081, China.
Stem Cell Res Ther. 2024 Sep 15;15(1):305. doi: 10.1186/s13287-024-03928-5.
Fibrosis with unrelieved chronic inflammation is an important pathological change in keloids. Mitochondrial autophagy plays a crucial role in reducing inflammation and inhibiting fibrosis. Adipose stem cell-derived exosomes, a product of adipose stem cell paracrine secretion, have pharmacological effects, such as anti-inflammatory and antiapoptotic effects, and mediate autophagy. Therefore, this study aims to investigate the function and mechanism of adipose stem cell exosomes in the treatment of keloids.
We isolated adipose stem cell exosomes under normoxic and hypoxic condition to detect their effects on keloid fibroblast proliferation, migration, and collagen synthesis. Meanwhile, 740YPDGFR (PI3K/AKT activator) was applied to detect the changes in autophagic flow levels and mitochondrial morphology and function in keloid fibroblasts. We constructed a human keloid mouse model by transplanting human keloid tissues into six-week-old (20-22 g; female) BALB/c nude mice, meanwhile, we applied adipose stem cell exosomes to treat the mouse model and observed the retention and effect of ADSC exosomes in vivo.
ADSC exosomes can inhibit the PI3K/AKT/mTOR signaling pathway. The exosomes of ADSCs decreased the inflammatory level of KFs, enhanced the interaction between P62 and LC3, and restored the mitochondrial membrane potential. In the human keloid mouse model, ADSC exosomes can exist stably, promote mitochondrial autophagy in keloid tissue, improve mitochondrial morphology, reduce inflammatory reaction and fibrosis. Meanwhile, At the same time, the exosomes derived from hypoxic adipose stem cells have played a more effective role in both in vitro and in vivo experiments.
Adipose stem cell exosomes inhibited the PI3K/AKT/mTOR pathway, activated mitochondrial autophagy, and alleviated keloid scars.
伴有慢性炎症未得到缓解的纤维化是瘢痕疙瘩的重要病理改变。线粒体自噬在减轻炎症和抑制纤维化方面起着至关重要的作用。脂肪干细胞衍生的外泌体是脂肪干细胞旁分泌的产物，具有抗炎和抗凋亡作用，并介导自噬。因此，本研究旨在探讨脂肪干细胞外泌体在治疗瘢痕疙瘩中的作用和机制。
我们在常氧和低氧条件下分离脂肪干细胞外泌体，以检测其对瘢痕成纤维细胞增殖、迁移和胶原合成的影响。同时，应用 740YPDGFR（PI3K/AKT 激活剂）检测瘢痕成纤维细胞中自噬流水平和线粒体形态及功能的变化。我们通过将人瘢痕组织移植到 6 周龄（20-22g；雌性）BALB/c 裸鼠中构建人瘢痕疙瘩小鼠模型，同时应用脂肪干细胞外泌体治疗小鼠模型，观察 ADSC 外泌体在体内的滞留和作用。
ADSC 外泌体可以抑制 PI3K/AKT/mTOR 信号通路。ADSCs 的外泌体降低了 KFs 的炎症水平，增强了 P62 和 LC3 之间的相互作用，并恢复了线粒体膜电位。在人瘢痕疙瘩小鼠模型中，ADSC 外泌体可以稳定存在，促进瘢痕组织中线粒体自噬，改善线粒体形态，减少炎症反应和纤维化。同时，在体外和体内实验中，来源于低氧脂肪干细胞的外泌体发挥了更有效的作用。
脂肪干细胞外泌体抑制了 PI3K/AKT/mTOR 通路，激活了线粒体自噬，减轻了瘢痕疙瘩。
