“Smart Exosomes”: A Smart Approach for Tendon Regeneration

Fang, William; Agrawal, Devendra K.; Thankam, Finosh G.

doi:10.1089/ten.teb.2021.0075

Cited by 21 publications

(28 citation statements)

References 120 publications

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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%

“…Additionally, several studies have indicated that exosomes inhibit the expression of various pro-inflammatory mediators and cytokines, including NF-kB, IL-1β, IL-6, IL-8, IL-18, COX-2, MMP1, MMP3 MMP9, iNOS, CXCL, IFNγ, and TNFα, leading to attenuated inflammation, which is ideal for tendon regeneration [ 56 , 57 , 59 , 61 , 63 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 ]. Zhang et al observed dramatically suppressed COX-2 factor in the TSC-Exos treatment group [ 63 ].…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

“…The team suggested that the decreased synthesis of proinflammatory cytokines might have been achieved by the AMPK signaling pathway, suppressing Wnt/b-catenin activity [ 73 ]. Studies have revealed that diseased tendons possessed stromal cells with elevated expressions of proinflammatory genes compared with healthy tendons [ 56 , 75 , 76 ]. Therefore, triggering and augmenting the expression of various anti-inflammatory or pro-resolving mediators is fundamentally beneficial for tendon repair and regeneration.…”

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

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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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Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

Section: Exosomes In Tendon and Repair And Regenerationmentioning

confidence: 99%

See 1 more Smart Citation

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Wan

Hussain

Behfar

et al. 2022

IJMS

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“…The concept of “Smart Exosomes” describes the manipulation, programming, and re-programming of the exosome and secretome contents to facilitate the management of tendon injury [ 145 ]. These smart exosomes act in the bone–tendon interface to regulate the pro-inflammatory to the anti-inflammatory environment, improve the biomechanical properties, and enhance proliferation, migration, and differentiation of tenocytes [ 145 ].…”

Section: Future Prospects 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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“…Also, the involvement of various EAT‐derived signals in myocardial inflammation/regeneration has been unveiled (Ege, 2020; Wu et al., 2017). Similar to any other adipose tissues, EAT acts as a stem cell‐rich niche, accelerating regenerative responses via paracrine, adipocrine, and vasocrine signaling mediated through exosomes (Fang et al., 2021; García‐Manrique et al., 2018; Gui et al., 2021). The potential effect of the epicardial adipose tissue derived stem cells (EATDS) and EATDS‐derived exosomes in eliciting cardioprotective responses has not been addressed.…”

Section: Introductionmentioning

confidence: 99%

Exosomal‐ribosomal proteins‐driven heterogeneity of epicardial adipose tissue derived stem cells under ischemia for cardiac regeneration

Thankam

Huynh

Fang

et al. 2022

J Tissue Eng Regen Med

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Extracellular ribosomal proteins secreted in exosomes elicit biological/regenerative responses; however, ribosomal proteins contained in the exosomes of ischemiachallenged epicardial adipose tissue-derived stem cells (EATDS) remain unexplored. This study focuses on the identification of ribosomal proteins in the exosomes of ischemia-challenged EATDS and their sub-populations based on the key ribosomal proteins using single-cell genomics. Exosomes were isolated from control, ischemic (ISC), and reperfused (ISC/R) EATDS harvested from hyperlipidemic microswine, and the proteins were detected using Liquid chromatography with tandem mass spectrometry (LC-MS/MS). One hundred ninety-nine proteins and 177 proteins were detected in ISC and ISC/R groups, respectively with significant fold-change compared to controls. Five ribosomal proteins, RPL10A, 40SRPS18, 40SRPS30, 60SRPL14, and 40SRPSA, were significant owing to their abundance based on LC-MS/MS data. Expression of these proteins, except RPL10A, at transcript and protein levels were lower in ISC group compared to the control. scRNAseq analysis revealed EATDS heterogeneity based on the upregulation of 40SRPSA, 40SRPL18, and 40SRPS18. Pro-inflammatory sub-populations upregulated CCL5, anti-inflammatory sub-population upregulated IL-11, proliferative sub-population upregulated cell cycle and DNA replication mediators, and nonproliferative population downregulated the cell cycle and DNA replication mediators. Overall, the functional role of extracellular ribosomal proteins in driving unique phenotypes of EATDS population offers promise for designing effective translational approaches for myocardial regeneration.

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“Smart Exosomes”: A Smart Approach for Tendon Regeneration

Cited by 21 publications

References 120 publications

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

The Therapeutic Potential of Exosomes in Soft Tissue Repair and Regeneration

Application of Orthobiologics in Achilles Tendinopathy: A Review

Exosomal‐ribosomal proteins‐driven heterogeneity of epicardial adipose tissue derived stem cells under ischemia for cardiac regeneration

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