Therapeutic potential of stem cell-derived extracellular vesicles in osteoarthritis: preclinical study findings

Kim, Ki Hoon; Jo, Jeong Hyun; Cho, Hye Jin; Park, Tae Sub; Kim, Tae Min

doi:10.1186/s42826-020-00043-3

Cited by 14 publications

(14 citation statements)

References 58 publications

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“…Delivery of the loading bioactive factors to cartilage is essential for MSC‐sEVs based OA therapy, which requires effective biodistribution of intra‐articularly injected sEVs in cartilage tissue (K. H. Kim, Jo, et al., 2020 ; Mancuso et al., 2019 ). The cartilage distribution of the solutes in synovial fluid was depends on two competing rates, namely the cartilage entering rate N Entry and the clearance rate by lymphatics and sub‐synovial capillaries N Exit (Bajpayee & Grodzinsky, 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…To overcome the hinderance, a surface charge reversing strategy of MSC-sEVs is raised in this study for OA treatment for the first time. Delivery of the loading bioactive factors to cartilage is essential for MSC-sEVs based OA therapy, which requires effective biodistribution of intra-articularly injected sEVs in cartilage tissue (K. H. Kim, Jo, et al, 2020;Mancuso et al, 2019). The cartilage distribution of the solutes in synovial fluid was depends on two competing rates, namely the cartilage entering rate N Entry and the (Bajpayee & Grodzinsky, 2017).…”

Section:  Discussionmentioning

confidence: 99%

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Reversing the surface charge of MSC‐derived small extracellular vesicles by εPL‐PEG‐DSPE for enhanced osteoarthritis treatment

Feng

Xie

Yuan

et al. 2021

J of Extracellular Vesicle

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Mesenchymal stem cell‐derived small extracellular vesicles (MSC‐sEVs) possess a great therapeutical potential for osteoarthritis (OA) treatment. However, the steric and electrostatic hindrance of cartilage matrix leads to very limited distribution of MSC‐sEVs in cartilage and low bioavailability of MSC‐sEVs after intra‐articular injection. To overcome this, a strategy to reverse the surface charge of MSC‐sEVs by modifying the MSC‐sEVs with a novel cationic amphiphilic macromolecule namely ε‐polylysine‐polyethylene‐distearyl phosphatidylethanolamine (PPD) was developed in this study. Through incubation with 100 μg/ml PPD, positively charged MSC‐sEVs (PPD‐sEVs) were obtained, and the modification process showed nearly no disturbance to the integrity and contents of sEVs and exhibited good stability under the interference of anionic macromolecules. A more effective cellular uptake and homeostasis modulation ability of PPD‐sEVs than unmodified MSC‐sEVs to chondrocytes was demonstrated. More importantly, PPD‐sEVs demonstrated significantly enhanced cartilage uptake, cartilage penetration, and joint retention capacity as compared to MSC‐sEVs. Intra‐articular injection of PPD‐sEVs into a mouse OA model showed significantly improved bioavailability than MSC‐sEVs, which resulted in enhanced therapeutic efficacy with reduced injection frequency. In general, this study provides a facile and effective strategy to improve the intra‐articular bioavailability of MSC‐sEVs and has a great potential to accelerate the clinical practice of MSC‐sEVs based OA therapy.

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Section: Discussionmentioning

confidence: 99%

Section:  Discussionmentioning

confidence: 99%

Reversing the surface charge of MSC‐derived small extracellular vesicles by εPL‐PEG‐DSPE for enhanced osteoarthritis treatment

Feng

Xie

Yuan

et al. 2021

J of Extracellular Vesicle

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“…In vivo experiments showed that the 3D-printed scaffolds significantly promoted cartilage regeneration [ 158 ]. In vitro mechanistic studies showed that EVs derived from MSCs mediate cartilage repair by enhancing proliferation, reducing cell apoptosis, and regulating the immune response [ 159 ].…”

Section: Composition and Characteristics Of Stem Cell Derivatives mentioning

confidence: 99%

Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

Jiang

Tian

et al. 2021

Stem Cells International

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Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.

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“…However, it has been demonstrated that BM-MSCs can exert protective effects through their paracrine mechanisms [ 17 , 84 , 85 , 86 , 87 ]. While previously it was thought that MSCs directly and actively participated in the tissue repair and regeneration process, there is increasing evidence that MSCs do not engraft within tissue [ 88 ]. It has been demonstrated that the majority of tissue protective effects of MSCs are exerted via paracrine signaling mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

Eshraghi

Ocak

Zhu

et al. 2020

JCM

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Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

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Therapeutic potential of stem cell-derived extracellular vesicles in osteoarthritis: preclinical study findings

Cited by 14 publications

References 58 publications

Reversing the surface charge of MSC‐derived small extracellular vesicles by εPL‐PEG‐DSPE for enhanced osteoarthritis treatment

Reversing the surface charge of MSC‐derived small extracellular vesicles by εPL‐PEG‐DSPE for enhanced osteoarthritis treatment

Research Progress on Stem Cell Therapies for Articular Cartilage Regeneration

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

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