Extracellular Vesicles Derived from Auricular Chondrocytes Facilitate Cartilage Differentiation of Adipose-Derived Mesenchymal Stem Cells

Purpose 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-beta 3) 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. Results 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-beta 3. 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. Conclusions 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. No Level Assigned This journal requires that authors 42 assign a level of evidence to each submission to which 43 Evidence-Based Medicine rankings are applicable. This 44 excludes Review Articles, Book Reviews, and manuscripts 45 that concern Basic Science, Animal Studies, Cadaver 46 Studies, and Experimental Studies. For a full description of 47 these Evidence-Based Medicine ratings, please refer to the 48 Table oof Contents or the online Instructions to Authors 49 .