Harnessing Tissue-derived Extracellular Vesicles for Osteoarthritis Theranostics

Abstract

Osteoarthritis (OA) is a prevalent chronic whole-joint disease characterized by low-grade systemic inflammation, degeneration of joint-related tissues such as articular cartilage, and alteration of bone structures that can eventually lead to disability. Emerging evidence has indicated that synovium or articular cartilage-secreted extracellular vesicles (EVs) contribute to OA pathogenesis and physiology, including transporting and enhancing the production of inflammatory mediators and cartilage degrading proteinases. Bioactive components of EVs are known to play a role in OA include microRNA, long non-coding RNA, and proteins. Thus, OA tissues-derived EVs can be used in combination with advanced nanomaterial-based biosensors for the diagnostic assessment of OA progression. Alternatively, mesenchymal stem cell- or platelet-rich plasma-derived EVs (MSC-EVs or PRP-EVs) have high therapeutic value for treating OA, such as suppressing the inflammatory immune microenvironment, which is often enriched by pro-inflammatory immune cells and cytokines that reduce chondrocytes apoptosis. Moreover, those EVs can be modified or incorporated into biomaterials for enhanced targeting and prolonged retention to treat OA effectively. In this review, we explore recently reported OA-related pathological biomarkers from OA joint tissue-derived EVs and discuss the possibility of current biosensors for detecting EVs and EV-related OA biomarkers. We summarize the applications of MSC-EVs and PRP-EVs and discuss their limitations for cartilage regeneration and alleviating OA symptoms. Additionally, we identify advanced therapeutic strategies, including engineered EVs and applying biomaterials to increase the efficacy of EV-based OA therapies. Finally, we provide our perspective on the future of EV-related diagnosis and therapeutic potential for OA treatment.

MSC-ACE2 Ameliorates Streptococcus uberis-Induced Inflammatory Injury in Mammary Epithelial Cells by Upregulating the IL-10/STAT3/SOCS3 Pathway

“…An increasing number of studies have shown that MSC has anti-apoptosis and cell proliferation-promoting effects ( 36 – 39 ). Apoptosis is divided into extrinsic (death receptor-mediated) and intrinsic (mitochondria-dependent) apoptotic pathways, which trigger the activation of downstream effector Caspase-3 through a series of signal transduction and ultimately initiate apoptosis ( 40 – 42 ).…”

AKR1B10, One of the Triggers of Cytokine Storm in SARS-CoV2 Severe Acute Respiratory Syndrome

“…In order to test this hypothesis, EVs were extracted from H1299 cells expressing different levels of AKR1B10 GFP (Low to High, see Supplementary Figure S1A for details), and levels of AKR1B10 in these EVs were estimated by Western blots (Figure 4A). Extraction by ultracentrifugation allowed for the sorting of EVs into two sub populations, the large EV, mainly composed of apoptotic bodies and microvesicles, and the Exosomes corresponding to small EVs with a diameter under 150 nm [33]. In order to test the possibility of the AKR1B10 GFP protein to be transferred between cell types, we exposed non-transfected RAW264.7 cells to EVs from H1299 cells, either expressing high levels of AKR1B10 GFP (H1299 High ) or without AKR1B10 GFP transfection (H1299 Ct ), and measured the GFP signal by FACS (Figure 4B).…”

The Role of Platelet-Derived Extracellular Vesicles in Immune-Mediated Thrombosis

“…The types of cells in the synovial fluid reflect the disease etiology, whether there is inflammatory arthropathy (sepsis, gout), or rheumatoid disease vs. an injury to the joint [ 113 ]. In RA, PEVs can leak into the synovial fluid, providing TF and a phospholipid surface on which the thrombin clot can form [ 57 , 134 , 152 , 154 ]. The PEVs that enter into the synovial fluid of RA patients contain more mitochondria and hyaluronan than the PEVs in osteoarthritis patients [ 35 , 155 ].…”