Adipose-derived mesenchymal stromal cell-derived exosomes promote tendon healing by activating both SMAD1/5/9 and SMAD2/3

Liu, Hengchen; Zhang, Mingzhao; Shi, Manyu; Zhang, Tingting; Lu, Wenjun; Yang, Shaoyu; Cui, Qingbo; Li, Zhaozhu

doi:10.1186/s13287-021-02410-w

Cited by 52 publications

(87 citation statements)

References 48 publications

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“…Besides, ADSC exosomes have also been found to activate the SMAD signaling pathway in tendon healing ( Liu et al, 2021a ), which is consistent with the above findings that SMAD transduction is upregulated by BMSC and USC exosomes. Thus, further analysis should be expanded about the SMAD signaling pathway via ADSC exosomes in the treatment of IDD, and the correlations between SMAD and other different sources of exosomes should also be further observed.…”

Section: Potential Sources Of Applications By Exosomes During the Pro...supporting

confidence: 86%

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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Low back pain (LBP), which is one of the most severe medical and social problems globally, has affected nearly 80% of the population worldwide, and intervertebral disc degeneration (IDD) is a common musculoskeletal disorder that happens to be the primary trigger of LBP. The pathology of IDD is based on the impaired homeostasis of catabolism and anabolism in the extracellular matrix (ECM), uncontrolled activation of immunologic cascades, dysfunction, and loss of nucleus pulposus (NP) cells in addition to dynamic cellular and biochemical alterations in the microenvironment of intervertebral disc (IVD). Currently, the main therapeutic approach regarding IDD is surgical intervention, but it could not considerably cure IDD. Exosomes, extracellular vesicles with a diameter of 30–150 nm, are secreted by various kinds of cell types like stem cells, tumor cells, immune cells, and endothelial cells; the lipid bilayer of the exosomes protects them from ribonuclease degradation and helps improve their biological efficiency in recipient cells. Increasing lines of evidence have reported the promising applications of exosomes in immunological diseases, and regarded exosomes as a potential therapeutic source for IDD. This review focuses on clarifying novel therapies based on exosomes derived from different cell sources and the essential roles of exosomes in regulating IDD, especially the immunologic strategy.

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Section: Potential Sources Of Applications By Exosomes During the Pro...supporting

confidence: 86%

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

Zhang

Wang

et al. 2022

Front. Cell Dev. Biol.

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“…During extrinsic healing, inflammatory cells and fibroblasts migrate from surrounding tissues, such as the sheath and synovium, to react in the initial inflammatory phase in the healing process [ 52 , 53 ]. Growth factors and cytokines released by the inflammatory cells during the initial phase play a dominant role in directing stem cell differentiation, tenocyte proliferation, and neo-tendon maturation in the later proliferative and regenerative phase [ 54 , 55 , 56 , 57 ]. Existing studies have shown encouraging anti-inflammatory and anti-scarring properties of exosomes in extrinsic healing of tendons.…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

“…Existing studies have shown encouraging anti-inflammatory and anti-scarring properties of exosomes in extrinsic healing of tendons. One of the most well-recognized mechanisms of exosomes is their capability of facilitating macrophage polarization and maintaining a dominant M2 pattern via paracrine [ 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 ].…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Wan

Hussain

Behfar

et al. 2022

IJMS

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Soft tissue defects are common following trauma and tumor extirpation. These injuries can result in poor functional recovery and lead to a diminished quality of life. The healing of skin and muscle is a complex process that, at present, leads to incomplete recovery and scarring. Regenerative medicine may offer the opportunity to improve the healing process and functional outcomes. Barriers to regenerative strategies have included cost, regulatory hurdles, and the need for cell-based therapies. In recent years, exosomes, or extracellular vesicles, have gained tremendous attention in the field of soft tissue repair and regeneration. These nanosized extracellular particles (30–140 nm) can break the cellular boundaries, as well as facilitate intracellular signal delivery in various regenerative physiologic and pathologic processes. Existing studies have established the potential of exosomes in regenerating tendons, skeletal muscles, and peripheral nerves through different mechanisms, including promoting myogenesis, increasing tenocyte differentiation and enhancing neurite outgrowth, and the proliferation of Schwann cells. These exosomes can be stored for immediate use in the operating room, and can be produced cost efficiently. In this article, we critically review the current advances of exosomes in soft tissue (tendons, skeletal muscles, and peripheral nerves) healing. Additionally, new directions for clinical applications in the future will be discussed.

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“…Transplantation of BM-MSC-derived EVs promotes tendon healing in rat model AT in a dose-dependent manner with the organization of tendon fibers, architecture, and type 1 collagen [ 137 ]. AD-MSC-derived Exos enhance tenogenic differentiation of TSCs and reduce inflammation through SMAD2/3 and SMAD1/5/9 signaling pathways [ 138 ]. AD-MSC-derived Exos enhance the proliferation of CD146 + TSCs.…”

Section: Orthobiologics In Atmentioning

confidence: 99%

Application of Orthobiologics in Achilles Tendinopathy: A Review

Ramires

Jeyaraman

Muthu

et al. 2022

Life

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Orthobiologics are biological materials that are intended for the regeneration of bone, cartilage, and soft tissues. In this review, we discuss the application of orthobiologics in Achilles tendinopathy, more specifically. We explain the concepts and definitions of each orthobiologic and the literature regarding its use in tendon disorders. The biological potential of these materials can be harnessed and administered into injured tissues, particularly in areas where standard healing is disrupted, a typical feature of Achilles tendinopathy. These products contain a wide variety of cell populations, cytokines, and growth factors, which have been shown to modulate many other cells at local and distal sites in the body. Collectively, they can shift the state of escalated inflammation and degeneration to reestablish tissue homeostasis. The typical features of Achilles tendinopathy are failed healing responses, persistent inflammation, and predominant catabolic reactions. Therefore, the application of orthobiologic tools represents a viable solution, considering their demonstrated efficacy, safety, and relatively easy manipulation. Perhaps a synergistic approach regarding the combination of these orthobiologics may promote more significant clinical outcomes rather than individual application. Although numerous optimistic results have been registered in the literature, additional studies and clinical trials are still highly desired to further illuminate the clinical utility and efficacy of these therapeutic strategies in the management of tendinopathies.

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Adipose-derived mesenchymal stromal cell-derived exosomes promote tendon healing by activating both SMAD1/5/9 and SMAD2/3

Cited by 52 publications

References 48 publications

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

Exosomes Immunity Strategy: A Novel Approach for Ameliorating Intervertebral Disc Degeneration

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Application of Orthobiologics in Achilles Tendinopathy: A Review

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