Exosomes derived from magnetically actuated bone mesenchymal stem cells promote tendon-bone healing through the miR-21-5p/SMAD7 pathway

Wu, Xiangdong; Kang, Lin; Tian, Jingjing; Wu, Yuanhao; Huang, Yue; Liu, Jieying; Wang, Hai; Qiu, Guixing; Wu, Zhihong

doi:10.1016/j.mtbio.2022.100319

Cited by 20 publications

(63 citation statements)

References 91 publications

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“…It solves the problem that MSCs from different sources can be applied to promote tendon-bone healing. In addition, studies have found that MSCs exercise their immunomodulatory biological functions by secreting exosomes, and researchers have attempted to use MSC-Exos to promote tendon-bone healing ( Wu et al, 2022a ; Xu et al, 2022a ; Li et al, 2022 ), results in animal models also showed good efficacy. Therefore, the application of the above MSCs optimization strategies in clinical studies should be widely carried out to accelerate the clinical application of the above strategies.…”

Section: Discussion and Outlookmentioning

confidence: 99%

“…It has been found that MSCs perform their biological functions such as promoting bone formation by secreting exosomes ( Wu et al, 2022a ; Xu et al, 2022a ; Han et al, 2022 ; Li et al, 2022 ). Therefore, mesenchymal stem cells-derived exosomes (MSC-Exos) have been widely investigated as a promising strategy for tissue regeneration.…”

Section: Preclinical Study Of Strategies To Promote Tendon-bone Heali...mentioning

confidence: 99%

“…The results also suggest that IPFP-MSC-Exos accelerates tendon-bone healing and intraarticular graft reconstruction after ACL reconstruction by participating in immune regulation of macrophage polarization. Recently, Wu et al (2022a) developed a new type of bone mesenchymal stem cell-derived exosomes (ION- Exos) driven by magnetic (iron oxide nanoparticle magnetic field, ION) to investigate whether ION- Exos play a more significant role than normal MSCs derived exosomes (MSC-Exos) in tenoon-bone healing. The results showed that IONP-Exos significantly prevented bone loss around the bone tunnel, promoted more bone inward growth in the tendon graft, increased fibrochondrogenesis at the tendon-bone tunnel interface, and induced a higher maximum failure load than MSC-Exos.…”

Section: Preclinical Study Of Strategies To Promote Tendon-bone Heali...mentioning

confidence: 99%

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Strategies to promote tendon-bone healing after anterior cruciate ligament reconstruction: Present and future

Tian

Zhang

Kang

2023

Front. Bioeng. Biotechnol.

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At present, anterior cruciate ligament (ACL) reconstruction still has a high failure rate. Tendon graft and bone tunnel surface angiogenesis and bony ingrowth are the main physiological processes of tendon-bone healing, and also the main reasons for the postoperative efficacy of ACL reconstruction. Poor tendon-bone healing has been also identified as one of the main causes of unsatisfactory treatment outcomes. The physiological process of tendon-bone healing is complicated because the tendon-bone junction requires the organic fusion of the tendon graft with the bone tissue. The failure of the operation is often caused by tendon dislocation or scar healing. Therefore, it is important to study the possible risk factors for tendon-bone healing and strategies to promote it. This review comprehensively analyzed the risk factors contributing to tendon-bone healing failure after ACL reconstruction. Additionally, we discuss the current strategies used to promote tendon-bone healing following ACL reconstruction.

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Section: Discussion and Outlookmentioning

confidence: 99%

Section: Preclinical Study Of Strategies To Promote Tendon-bone Heali...mentioning

confidence: 99%

Section: Preclinical Study Of Strategies To Promote Tendon-bone Heali...mentioning

confidence: 99%

See 1 more Smart Citation

Strategies to promote tendon-bone healing after anterior cruciate ligament reconstruction: Present and future

Tian

Zhang

Kang

2023

Front. Bioeng. Biotechnol.

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“…In a seminal study, Cui et al reported that macrophage-derived miR-21-5p-containing exosomes induced peritendinous fibrosis after tendon injury by directly targeting Smad7 in a rat model [ 86 ]. Interestingly, it has recently been found that exosomal miR-21-5p could promote fibrogenesis and enhance tendon-bone integration by reducing SMAD7 expression levels in a rat model of ACLR [ 88 ]. Furthermore, Feng et al discovered that exosomes derived from genetically modified Scleraxis-overexpressing PDGFRα(+) BMMSCs delivered miR-6924–5p to prevent osteoclast formation during tendon–bone healing and enhance the biomechanical strength of the TBI [ 89 ].…”

Section: Current Progress In the Application Of Exosomes To Tbi Injuriesmentioning

confidence: 99%

Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon–bone healing

et al. 2023

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Tendon–bone insertion (TBI) injuries, such as anterior cruciate ligament injury and rotator cuff injury, are the most common soft tissue injuries. In most situations, surgical tendon/ligament reconstruction is necessary for treating such injuries. However, a significant number of cases failed because healing of the enthesis occurs through scar tissue formation rather than the regeneration of transitional tissue. In recent years, the therapeutic potential of mesenchymal stem cells (MSCs) has been well documented in animal and clinical studies, such as chronic paraplegia, non-ischemic heart failure, and osteoarthritis of the knee. MSCs are multipotent stem cells, which have self-renewability and the ability to differentiate into a wide variety of cells such as chondrocytes, osteoblasts, and adipocytes. Numerous studies have suggested that MSCs could promote angiogenesis and cell proliferation, reduce inflammation, and produce a large number of bioactive molecules involved in the repair. These effects are likely mediated by the paracrine mechanisms of MSCs, particularly through the release of exosomes. Exosomes, nano-sized extracellular vesicles (EVs) with a lipid bilayer and a membrane structure, are naturally released by various cell types. They play an essential role in intercellular communication by transferring bioactive lipids, proteins, and nucleic acids, such as mRNAs and miRNAs, between cells to influence the physiological and pathological processes of recipient cells. Exosomes have been shown to facilitate tissue repair and regeneration. Herein, we discuss the prospective applications of MSC-derived exosomes in TBI injuries. We also review the roles of MSC–EVs and the underlying mechanisms of their effects on promoting tendon–bone healing. At last, we discuss the present challenges and future research directions. Graphical Abstract

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“…27 The performance of exosomes needs to be optimized by endowing them with stronger specific effects. Recently, Wu et al 36 reported that exosomes derived from magnetically actuated BMSCs had more significant effects on tendon-tobone healing than BMSC-derived exosomes. Feng et al 11 found that exosomes derived from genetically modified Scleraxis-overexpressing PDGFRa( 1 ) BMSCs could reduce osteolysis during tendon-bone healing.…”

mentioning

confidence: 99%

Exosomes Derived From Kartogenin-Preconditioned Mesenchymal Stem Cells Promote Cartilage Formation and Collagen Maturation for Enthesis Regeneration in a Rat Model of Chronic Rotator Cuff Tear

Cai

et al. 2023

Am J Sports Med

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Background: Poor tendon-to-bone healing in chronic rotator cuff tears (RCTs) is related to unsatisfactory outcomes. Exosomes derived from mesenchymal stem cells reportedly enhance rotator cuff healing. However, the difficulty in producing exosomes with a stronger effect on enthesis regeneration must be resolved. Purpose: To study the effect of exosomes derived from kartogenin (KGN)-preconditioned human bone marrow mesenchymal stem cells (KGN-Exos) on tendon-to-bone healing in a rat model of chronic RCT. Study Design: Controlled laboratory study. Methods: Exosome-loaded sodium alginate hydrogel (SAH) was prepared. Moreover, exosomes were labeled with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindotricarbocyanine iodide (DiR) or 1,1′-dioctadecyl-3,3,3′3′-tetramethylindocarbocyanine perchlorate (Dil) for in vivo tracking. Bilateral rotator cuff repair (RCR) was conducted in an established chronic RCT rat model. A total of 66 rats were randomized to control, untreated exosome (un-Exos), and KGN-Exos groups to receive local injections of pure SAH, un-Exos, or KGN-Exos SAH at the repaired site. The presence of DiR/Dil-labeled exosomes was assessed at 1 day and 1 week, and tendon-to-bone healing was evaluated histologically, immunohistochemically, and biomechanically at 4 and 8 weeks. Results: Both un-Exos and KGN-Exos exhibited sustained release from SAH for up to 96 hours. In vivo study revealed that un-Exos and KGN-Exos were localized to the repaired site at 1 week. Moreover, the KGN-Exos group showed a higher histological score and increased glycosaminoglycan and collagen II expression at 4 and 8 weeks. In addition, more mature and better-organized collagen fibers with higher ratios of collagen I to collagen III were observed at 8 weeks in the tendon-to-bone interface compared with those in the control and un-Exos groups. Biomechanically, the KGN-Exos group had the highest failure load (28.12 ± 2.40 N) and stiffness (28.57 ± 2.49 N/mm) among the 3 groups at 8 weeks. Conclusion: Local injection of SAH with sustained KGN-Exos release could effectively promote cartilage formation as well as collagen maturation and organization for enthesis regeneration, contributing to enhanced biomechanical properties after RCR. Clinical Relevance: KGN-Exos injection may be used as a cell-free therapeutic option to accelerate tendon-to-bone healing in chronic RCT.

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Exosomes derived from magnetically actuated bone mesenchymal stem cells promote tendon-bone healing through the miR-21-5p/SMAD7 pathway

Cited by 20 publications

References 91 publications

Strategies to promote tendon-bone healing after anterior cruciate ligament reconstruction: Present and future

Strategies to promote tendon-bone healing after anterior cruciate ligament reconstruction: Present and future

Therapeutic potential and mechanisms of mesenchymal stem cell-derived exosomes as bioactive materials in tendon–bone healing

Exosomes Derived From Kartogenin-Preconditioned Mesenchymal Stem Cells Promote Cartilage Formation and Collagen Maturation for Enthesis Regeneration in a Rat Model of Chronic Rotator Cuff Tear

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