Adipose Stem Cell–Derived Exosomes Decrease Fatty Infiltration and Enhance Rotator Cuff Healing in a Rabbit Model of Chronic Tears

Wang, Chongyang; Hu, Qingxiang; Song, Wei; Yu, Weilin; He, Yaohua

doi:10.1177/0363546520908847

Cited by 83 publications

(131 citation statements)

References 38 publications

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“…However, Zhang et al 77 demonstrated the e cacy of human embryonic MSC exosomes in promoting cartilage regeneration, and the utility of MSC exosomes as a ready-to-use and "cell-free" therapeutic alternative to cell-based MSC therapy in vivo. As for BTI healing, Wang et al 71 showed that adipose stem cell-derived Exos can decrease fatty in ltration and enhance BTI healing in vivo. In accordance with Wang et al 71 research, the present study also revealed improved BTI healing which can be judged by the decrease of brous scar tissue formation, augment of brocartilaginous enthesis regeneration and better biomechanical properties.…”

Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Preconditioned by Low-Intensity Pulsed Ultrasound Stimulation Promote Bone-Tendon Interface Fibrocartilage Regeneration and Ameliorate Rotator Cuff Fatty Infiltration

Chen

Shi

et al. 2021

Preprint

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Fibrovascular scar healing of bone-tendon interface (BTI) instead of functional fibrocartilage regeneration is the main concern associated with unsatisfactory prognosis in rotator cuff repair. Mesenchymal stem cells exosomes have been reported to be a new promising cell-free approach for rotator cuff healing. Whereas, controvercies abound in whether exosomes of native MSCs alone can effectively induce chondrogenesis. In this study, we aimed to explore the effect of Exosomes derived from low-intensity pulsed ultrasound stimulation (LIPUS)-preconditioned bone marrow mesenchymal stem cells (LIPUS-BMSC-Exos) or un-preconditioned BMSCs (BMSC-Exos) on rotator cuff healing and the underlying mechanism. Specifically, C57BL/6 mice underwent unilateral supraspinatus tendon detachment and repair were randomly assigned to saline, BMSCs-Exos or LIPUS-BMSC-Exos injection therapy. The results indicated that the biomechanical properties of the supraspinatus tendon-humeral junction were significantly improved in the LIPUS-BMSC-Exos group than that of the BMSCs-Exos group. The LIPUS-BMSC-Exos group also exhibited a higher histological score and more newly regenerated fibrocartilage at the repair site at postoperative 2 and 4 weeks and less fatty infiltration at 4 weeks than the BMSCs-Exos group. In vitro, co-culture of BMSCs with LIPUS-BMSC-Exos could significantly promote BMSCs chondrogenic differentiation and inhibit adipogenic differentiation than the BMSCs and BMSC-Exos co-cultured group did. Subsequently, quantitative real-time polymerase chain reaction revealed significantly higher enrichment of chondrogenic miRNAs and less enrichment of adipogenic miRNAs in LIPUS-BMSC-Exos compared with BMSC-Exos. Moreover, we demonstrated that this chondrogenesis-inducing potential was primarily attributed to miR-140, one of the most abundant miRNAs in LIPUS-BMSC-Exos. Collectively, our results highlight the regenerative potential of LIPUS-BMSC-Exos to promote BTI fibrocartilage regeneration and ameliorate supraspinatus fatty infiltration by positive regulation of pro-chondrogenetic and anti-adipogenetic of BMSCs differentiation which was primarily through delivering miR-140.

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Section: Discussionmentioning

confidence: 99%

WITHDRAWN: Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Preconditioned by Low-Intensity Pulsed Ultrasound Stimulation Promote Bone-Tendon Interface Fibrocartilage Regeneration and Ameliorate Rotator Cuff Fatty Infiltration

Chen

Shi

et al. 2021

Preprint

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“…These cartilage protective findings of IPFP-Exos in DMM-induced OA are similar to the beneficial effects seen in a new study with ADSCs-Exos for chronic rotator cuff tears in a rabbit model, where lower fatty infiltration, more newly regenerated fibrocartilage, and improved biomechanics was seen in the ADSCs-Exos group compared to those with saline only [ 43 ].…”

Section: Resultssupporting

confidence: 79%

Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review

Gupta

Sgaglione

et al. 2021

JCM

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Osteoarthritis of the knee is one of the most common chronic, debilitating musculoskeletal conditions. Current conservative treatment modalities such as weight loss, non-steroidal anti-inflammatory drugs, and intra-articular steroid injections often only provide temporary pain relief and are unsatisfactory for long-term management. Though end stage osteoarthritis of the knee can be managed with total knee arthroplasty (TKA), finding alternative non-surgical options to delay or prevent the need for TKA are needed due to the increased healthcare costs and expenditures associated with TKA. Exosomes have been of particular interest given recent findings highlighting that stem cells may at least partially mediate some of their effects through the release of extracellular vesicles, such as exosomes. As such, better understanding the biological mechanisms and potential therapeutic effects of these exosomes is necessary. Here, we review in vivo studies that highlight the potential clinical use of exosomes derived from non-classical sources (not bone marrow or adipose derived MSCs derived MSCs) for osteoarthritis of the knee.

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“…ASC–conditioned medium (ASC-CM) was used to isolate ASC-Exos by gradient ultracentrifugation as our previous studies described. 25,26 Briefly, the ASC-CM was ultracentrifuged as follows: 300 g , 10 minutes (to remove the live cell pellet); 2000 g , 10 minutes (to remove the dead cell pellet); 10,000 g , 30 minutes (to remove the cell debris pellet); 100,000 g , 70 minutes (to obtain the ASC-Exos and contaminating protein pellet); and 100,000 g , 70 minutes (to obtain the ASC-Exos pellet).…”

Section: Methodsmentioning

confidence: 99%

Adipose Stem Cell–Derived Exosomes Ameliorate Chronic Rotator Cuff Tendinopathy by Regulating Macrophage Polarization: From a Mouse Model to a Study in Human Tissue

Wang

Zhang

et al. 2021

Am J Sports Med

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Background: Chronic rotator cuff (RC) tendinopathy is one of the most prevalent causes of shoulder pain. Growing evidence suggests that macrophages play a significant role in the proinflammatory response, resolution of inflammation, and tissue healing of tendinopathy. In particular, enhancement of M2 macrophage (M2φ) activity contributes to the accelerated healing of tendinopathy. Therefore, a treatment that enhances M2φ polarization would be useful for patients with this common musculoskeletal disorder. Purpose: To investigate whether adipose stem cell–derived exosomes (ASC-Exos) enhance M2φ polarization and ameliorate chronic RC tendinopathy. Study Design: Controlled laboratory study. Methods: First, we compared the effects of ASC-Exos on polarization of mouse bone marrow–derived macrophages between a classically activated phenotype (M1φ) and an alternatively activated phenotype (M2φ) in vitro. In total, 72 C57BL/6 mice were assigned to normal cage activity (n = 24) or 5 weeks of treadmill overuse (n = 48). The supraspinatus tendon of each treadmill overuse mouse was treated with ASC-Exos (n = 24) or saline (n = 24). Histological and biomechanical outcomes were assessed 4 weeks after treatment. Finally, tissue samples from human patients with RC tendinopathy were obtained to assay the effect of ASC-Exos on the M1φ/M2φ balance in tissue-resident macrophages. Results: ASC-Exos inhibited M1φ polarization and augmented M2φ polarization in vitro and in vivo. Mice in the ASC-Exos group showed less severe pathological changes than those in the saline group, including less cellular infiltration, disorganization of collagen, and ground substance deposition. The modified Bonar score of the ASC-Exos group (mean ± SD, 7.68 ± 1.03) was significantly lower than that of the saline group (9.81 ± 0.96; P < .05). Furthermore, the maximum failure load was significantly higher in the ASC-Exos group than in the saline group (4.23 ± 0.66 N vs 3.86 ± 0.65 N; P < .05), as was stiffness (3.38 ± 0.34 N/m vs 2.68 ± 0.49 N/m; P < .05). Conclusion: ASC-Exos–mediated polarization balance of M1φ/M2φ contributes to the amelioration of chronic RC tendinopathy. Regulation of the M1φ/M2φ balance could be a new target for the treatment of chronic RC tendinopathy. Clinical Relevance: Administration of ASC-Exos is a cell-free approach that may become a novel treatment option for chronic RC tendinopathy and should be explored further.

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Adipose Stem Cell–Derived Exosomes Decrease Fatty Infiltration and Enhance Rotator Cuff Healing in a Rabbit Model of Chronic Tears

Cited by 83 publications

References 38 publications

WITHDRAWN: Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Preconditioned by Low-Intensity Pulsed Ultrasound Stimulation Promote Bone-Tendon Interface Fibrocartilage Regeneration and Ameliorate Rotator Cuff Fatty Infiltration

WITHDRAWN: Exosomes Derived from Bone Marrow Mesenchymal Stem Cell Preconditioned by Low-Intensity Pulsed Ultrasound Stimulation Promote Bone-Tendon Interface Fibrocartilage Regeneration and Ameliorate Rotator Cuff Fatty Infiltration

Exosomes Derived from Non-Classic Sources for Treatment of Post-Traumatic Osteoarthritis and Cartilage Injury of the Knee: In Vivo Review

Adipose Stem Cell–Derived Exosomes Ameliorate Chronic Rotator Cuff Tendinopathy by Regulating Macrophage Polarization: From a Mouse Model to a Study in Human Tissue

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