Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 33 Badachu Road, Shijingshan District, Beijing, 100144, People's Republic of China.
Aesthetic Plast Surg. 2023 Dec;47(6):2823-2832. doi: 10.1007/s00266-023-03292-4. Epub 2023 Feb 27.
Adipose-derived mesenchymal stem cell (ADSC)-based therapies have been utilized for cartilage regeneration because of their multi-lineage differentiation ability. However, commonly used cartilage inducers such as the transforming growth factor beta-3 (TGF-β3) may be prone to cartilage dedifferentiation and hypertrophy. The directional differentiation of elastic cartilage is limited nowadays. Extracellular vesicles (EVs) have been reported to influence the specific differentiation of mesenchymal stem cells (MSCs) by reflecting the composition of the parental cells. However, the role of auricular chondrogenic-derived EVs (AC-EVs) in elastic chondrogenic differentiation of ADSCs has not yet been reported.
AC-EVs isolated from the external ears of swine exhibited a positive effect on cell proliferation and migration. Furthermore, AC-EVs efficiently promoted chondrogenic differentiation of ADSCs in pellet culture, as shown by the elevated levels of COL2A1, ACAN, and SOX-9 expression. Moreover, there was a significantly higher expression of elastin and a lower expression of the fibrotic marker COL1A1 in comparison with that achieved with TGF-β3. The staining results demonstrated that AC-EVs promoted the deposition of cartilage-specific matrix, which is in good concordance with the real-time polymerase chain reaction (RT-PCR) results.
Auricular chondrogenic-derived EVs are a crucial component in elastic chondrogenic differentiation and other biological behaviors of ADSCs, which may be a useful ingredient for cartilage tissue engineering and external ear reconstruction.
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脂肪间充质干细胞（ADSC）具有多向分化能力，已被用于软骨再生治疗。然而，常用的软骨诱导剂如转化生长因子-β3（TGF-β3）可能容易导致软骨去分化和肥大。目前弹性软骨的定向分化受到限制。细胞外囊泡（EVs）已被报道通过反映亲代细胞的组成来影响间充质干细胞（MSCs）的特异性分化。然而，耳软骨衍生的 EVs（AC-EVs）在 ADSC 弹性软骨分化中的作用尚未报道。
从猪外耳分离的 AC-EVs 表现出对细胞增殖和迁移的积极影响。此外，AC-EVs 在微球培养中有效地促进了 ADSC 的软骨分化，COL2A1、ACAN 和 SOX-9 的表达水平升高。此外，与 TGF-β3 相比，弹性蛋白的表达显著升高，纤维化标志物 COL1A1 的表达降低。染色结果表明，AC-EVs 促进了软骨特异性基质的沉积，这与实时聚合酶链反应（RT-PCR）结果非常吻合。
耳软骨衍生的 EVs 是 ADSC 弹性软骨分化和其他生物学行为的重要组成部分，可能是软骨组织工程和外耳重建的有用成分。
