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Updated: Jun 12, 2025
Labeling of Extracellular Vesicles for Monitoring Migration and Uptake in Cartilage Explants
Published on: October 4, 2021
M2 Macrophage-Derived Extracellular Vehicles-Loaded Hyaluronic Acid-Alginate Hydrogel for Treatment of Osteoarthritis
Wen Zhang1,2, Menghan Luo1,2, Yi Xing1,3
1Department of Orthodontics, Tianjin Medical University School and Hospital of Stomatology & Tianjin Key Laboratory of Oral Soft and Hard Tissues Restoration and Regeneration, Tianjin, People's Republic of China.
Objective:
Osteoarthritis (OA), a high-prevalence degenerative cartilage disease, urgently requires novel therapeutic strategies. M2 macrophage-derived exosomes (M2-Exo) demonstrate therapeutic potential for OA, though their regulatory mechanisms in chondrocyte-macrophage (Mφ) interactions remain to be elucidated. To investigate the regulatory effects of M2-Exo on chondrocytes and Mφ in vitro, and to evaluate the therapeutic effect of the M2-Exo-loaded hydrogel system (ALG-M2Exo) on cartilage damage in a rat OA model.
Methods:
In the cell experiment, M2-Exo were extracted and characterized using ultracentrifugation. Different concentrations of M2-Exo were co-cultured with inflammatory chondrocytes or M1Mφ to evaluate their direct anti-inflammatory effects and the ability to promote M1Mφ repolarization to the M2 phenotype, using methods such as EdU, TUNEL, qRT-PCR, and Western blot. Then, the repolarized RM2Mφ were co-cultured with inflammatory chondrocytes to verify their anti-inflammatory efficacy, employing similar detection methods. In the in vivo experiment, sodium iodoacetate was injected to establish a rat knee OA model, followed by interventions including ALG-M2Exo. After 4 and 8 weeks, samples were collected for gross observation and histological staining to assess cartilage damage repair.
Results:
In the cell experiment, M2-Exo exhibited typical exosomal characteristics, directly promoting the proliferation of inflammatory chondrocytes, inhibiting their apoptosis, reducing the expression of TNF-α, iNOS, and MMP-13, and increasing the expression of IL-10 and COL II. RM2Mφ showed similar therapeutic effects on inflammatory chondrocytes as M2-Exo. In the in vivo experiment, the ALG-M2Exo group demonstrated superior repair effects on cartilage damage compared to other groups, with the treatment effect at 8 weeks being better than at 4 weeks.
Conclusion:
ALG-M2Exo effectively promotes the repair of cartilage damage in OA through both a direct pathway by releasing M2-Exo that act on chondrocytes and an indirect pathway that facilitates the repolarization of M1Mφ to M2Mφ.
