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Clinical Protocol of Producing Adipose Tissue-Derived Stromal Vascular Fraction for Potential Cartilage Regeneration
Published on: September 29, 2018
Small extracellular vesicles from human adipose-derived stem cells attenuate cartilage degeneration
Chang Hee Woo1,2, Hark Kyun Kim3, Gun Young Jung3
1Department of Chemical Engineering, Hanyang University, Ansan, Korea.
Abstract:
Osteoarthritis (OA) is a chronic degenerative disease of articular cartilage that is the most common joint disease worldwide. Mesenchymal stem cells (MSCs) have been the most extensively explored for the treatment of OA. Recently, it has been demonstrated that MSC-derived extracellular vesicles (EVs) may contribute to the potential mechanisms of MSC-based therapies. In this study, we investigated the therapeutic potential of human adipose-derived stem cells EVs (hASC-EVs) in alleviating OA, along with the mechanism. EVs were isolated from the culture supernatants of hASCs by a multi-filtration system based on the tangential flow filtration (TFF) system. The isolated EVs were characterised using dynamic light scattering (DLS), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and flow cytometry analysis. The hASC-EVs not only promoted the proliferation and migration of human OA chondrocytes, but also maintained the chondrocyte matrix by increasing type Ⅱ collagen synthesis and decreasing MMP-1, MMP-3, MMP-13 and ADAMTS-5 expression in the presence of IL-1β in vitro. Intra-articular injection of hASC-EVs significantly attenuated OA progression and protected cartilage from degeneration in both the monosodium iodoacetate (MIA) rat and the surgical destabilisation of the medial meniscus (DMM) mouse models. In addition, administration of hASC-EVs inhibited the infiltration of M1 macrophages into the synovium. Overall results suggest that the hASC-EVs should be considered as a potential therapeutic approach in the treatment of OA.
Insights
Human adipose-derived stem cell extracellular vesicles (hASC-EVs) show promise for treating osteoarthritis (OA). These EVs promote cartilage health and reduce OA progression in preclinical models, offering a potential new therapy for this common joint disease.
Area of Science:
- Regenerative Medicine
- Biotechnology
- Orthopedics
Background:
- Osteoarthritis (OA) is a prevalent degenerative joint disease affecting articular cartilage.
- Mesenchymal stem cells (MSCs) are explored for OA treatment, with MSC-derived extracellular vesicles (EVs) emerging as key therapeutic agents.
- Human adipose-derived stem cells EVs (hASC-EVs) represent a promising cell-free therapeutic strategy for OA.
Purpose of the Study:
- To investigate the therapeutic potential of hASC-EVs in alleviating osteoarthritis.
- To elucidate the underlying mechanisms of hASC-EVs in OA treatment.
- To evaluate hASC-EVs efficacy in preclinical OA models.
Main Methods:
- EVs were isolated from hASCs using tangential flow filtration (TFF).
- hASC-EVs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry.
- In vitro studies involved human OA chondrocytes treated with IL-1β, while in vivo studies used monosodium iodoacetate (MIA) rat and destabilization of the medial meniscus (DMM) mouse models.
Main Results:
- hASC-EVs promoted OA chondrocyte proliferation and migration in vitro.
- hASC-EVs maintained chondrocyte matrix by increasing type II collagen and decreasing matrix-degrading enzymes (MMP-1, MMP-3, MMP-13, ADAMTS-5) in vitro.
- Intra-articular injection of hASC-EVs attenuated OA progression, protected cartilage, and inhibited M1 macrophage infiltration in vivo.
Conclusions:
- hASC-EVs demonstrate significant therapeutic potential for osteoarthritis treatment.
- hASC-EVs exert chondroprotective effects and modulate the inflammatory microenvironment in OA.
- hASC-EVs represent a viable cell-free therapeutic approach for managing osteoarthritis.
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