Stem-Cell Derived Exosomes for the Treatment of Osteoarthritis

Ke, Zekai; Zhu, Jinyu

doi:10.2174/1574888x15666200206104332

Cited by 7 publications

(4 citation statements)

References 38 publications

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“…Moreover, the chondroprotective effect of DPSCs-exosomes was achieved through delivering exosomal miR-31 to the treated area. Likewise, several studies have confirmed the significant role of miR-31in treating osteoarthritis [51]. This suggests that exosome-mediated injection of miR-31could play a pivotal role in regulating recipient cells functions and cell-to-cell signals.…”

Section: P R E P R I N Tmentioning

confidence: 80%

The Role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels

et al. 2023

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IntroductionOsteoarthritis is the most prevalent musculoskeletal progressive disease that leads to functional impairment and decreased quality of life. However, the current treatments remain unsatisfactory. Recent studies reveal that exosomes derived from mesenchymal stem cells offer a promising approach to improve the pathological changes of osteoarthritis, cartilage tissue, and chondrocyte homeostasis.Material and methodsA randomized, controlled animal experiment was conducted on nine-week-old male C57BL/6 mice that were obtained from Charles River Laboratories. In this in vitro and in vivo study, we studied the role and mechanisms of dental pulp stem cell-derived exosomes (DPSCs-exosomes) on osteoarthritis in the mouse model.ResultsThe study findings showed that a dental pulp stem cell could generate typical-characteristic exosomes. The injection of DPSCs-exosomes ameliorated destruction of cartilage, promoted matrix synthesis, inhibited cell apoptosis, and decreased the catabolic factors expression. However, this effect was shown to be almost eliminated when miR-31 antagomir was injected.ConclusionsFurthermore, DPSCs-exosomes show an ability to promote autophagy in chondrocytes through mTOR inhibition, in addition to reducing the mTOR luciferase activity. The ability of DPSCs-exosomes to partially regulate autophagy was blocked upon inhibition of miR-31. In brief, DPSCs-exosomes have a chondroprotective role in the mice osteoarthritis model. The underlying mechanism is possibly related to miR-31-mediated suppression of the mTOR-autophagy pathway.

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Section: P R E P R I N Tmentioning

confidence: 80%

The Role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels

et al. 2023

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“…The microcryogels can provide the MSCs with such a microenvironment and facilitate natural cell–cell and cell–ECM interactions, which can increase their paracrine secretions and result in a range of effects that are beneficial for cartilage repair, including cell homing, anti-inflammation, and immune regulation 41 – 43 . Moreover, the microcryogels containing accumulated ECM may better preserve the MSC-secreted exosomes to help suppress OA development 44 , 45 . The microcryogels may also offer physical protection to the MSCs by shielding them from mechanical insult and necrosis during and after cell injection 14 , 46 , 47 .…”

Section: Discussionmentioning

confidence: 99%

Intra-articular Injection of Cell-laden 3D Microcryogels Empower Low-dose Cell Therapy for Osteoarthritis in a Rat Model

et al. 2020

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Intra-articular injection of mesenchymal stem cells (MSCs) in an osteoarthritic joint can help slow down cartilage destruction. However, cell survival and the efficiency of repair are generally low due to mechanical damage during injection and a high rate of cell loss. We, thus, investigated an improved strategy for cell delivery to an osteoarthritic joint through the use of three-dimensional (3D) microcryogels. MSCs were seeded into 3D microcryogels. The viability and proliferation of MSCs in microcryogels were determined over 5 d, and the phenotype of MSCs was confirmed through trilineage differentiation tests and flow cytometry. In Sprague Dawley rats with induced osteoarthritis (OA) of the knee joint, a single injection was made with the following groups: saline control, low-dose free MSCs (1 × 105 cells), high-dose free MSCs (1 × 106 cells), and microcryogels + MSCs (1 × 105 cells). Cartilage degeneration was evaluated by macroscopic examination, micro-computed tomographic analysis, and histology. MSCs grown in microcryogels exhibited optimal viability and proliferation at 3 d with stable maintenance of phenotype in vitro. Microcryogels seeded with MSCs were, therefore, primed for 3 d before being used for in vivo experiments. At 4 and 8 wk, the microcryogels + MSCs and high-dose free MSC groups had significantly higher International Cartilage Repair Society macroscopic scores, histological evidence of more proteoglycan deposition and less cartilage loss accompanied by a lower Mankin score, and minimal radiographic evidence of osteoarthritic changes in the joint compared to the other two groups. In conclusion, intra-articular injection of cell-laden 3D microcryogels containing a low dose of MSCs can achieve similar effects as a high dose of free MSCs for OA in a rat model. Primed MSCs in 3D microcryogels can be considered as an improved delivery strategy for cell therapy in treating OA that minimizes cell dose while retaining therapeutic efficacy.

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“…In contrast to the prevalent application of platelet-rich plasma (PRP) in clinical settings, the development of exosome-based therapies is still preliminary, and studies are largely preclinical. Recent research has gradually demonstrated the therapeutic efficacy of exosomes in musculoskeletal healing [ 17 , 18 ]. Exosomes derived from adipose-derived stem cells (ADSC-Exos), for example, have been shown to promote human rotator cuff healing by inhibiting muscle atrophy and degeneration, while also improving the histological properties of the torn tendon [ 19 ].…”

Section: Molecular Mechanisms Of Exosomesmentioning

confidence: 99%

Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell-Derived Exosomes

Chen

Kao

Chen

et al. 2023

Cells

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Exosomes are effective therapeutic vehicles that may transport their substances across cells. They are shown to possess the capacity to affect cell proliferation, migration, anti-apoptosis, anti-scarring, and angiogenesis, via the action of transporting molecular components. Possessing immense potential in regenerative medicine, exosomes, especially stem cell-derived exosomes, have the advantages of low immunogenicity, minimal invasiveness, and broad clinical applicability. Exosome biodistribution and pharmacokinetics may be altered, in response to recent advancements in technology, for the purpose of treating particular illnesses. Yet, prior to clinical application, it is crucial to ascertain the ideal dose and any potential negative consequences of an exosome. This review focuses on the therapeutic potential of stem cell-derived exosomes and further illustrates the molecular mechanisms that underpin their potential in musculoskeletal regeneration, wound healing, female infertility, cardiac recovery, immunomodulation, neurological disease, and metabolic regulation. In addition, we provide a summary of the currently effective techniques for isolating exosomes, and describe the innovations in biomaterials that improve the efficacy of exosome-based treatments. Overall, this paper provides an updated overview of the biological factors found in stem cell-derived exosomes, as well as potential targets for future cell-free therapeutic applications.

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Stem-Cell Derived Exosomes for the Treatment of Osteoarthritis

Cited by 7 publications

References 38 publications

The Role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels

The Role and underlying mechanism of dental pulp stem cell-derived exosomal miR-31 in the treatment of osteoarthritis by targeting mTOR to enhance chondrocyte autophagy levels

Intra-articular Injection of Cell-laden 3D Microcryogels Empower Low-dose Cell Therapy for Osteoarthritis in a Rat Model

Frontier Review of the Molecular Mechanisms and Current Approaches of Stem Cell-Derived Exosomes

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