Reparative and Maladaptive Inflammation in Tendon Healing

Arvind, Varun; Huang, Alice H.

doi:10.3389/fbioe.2021.719047

Cited by 61 publications

(52 citation statements)

References 189 publications

(259 reference statements)

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“…Recent works have proved that tenocytes participate in the amplification of the inflammatory response after tendon damage through the secretion of different cytokines and chemokines [ 66 ]. On the other hand, IL-4 promotes the transformation of naive CD4 T cells and macrophages into a Th2 T cell or M2 macrophage phenotype, respectively, which drives the type 2 anti-inflammatory immune response [ 67 ]. Thus, it is plausible that tenocytes can also have a role in the modulation of the reparative (anti-inflammatory) immune response, which should be studied in future works.…”

Section: Resultsmentioning

confidence: 99%

Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model

Graça

Domingues

Calejo

et al. 2022

IJMS

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Tendon injuries represent over 30–50% of musculoskeletal disorders worldwide, yet the available therapies do not provide complete tendon repair/regeneration and full functionality restoring. Extracellular vesicles (EVs), membrane-enclosed nanoparticles, have emerged as the next breakthrough in tissue engineering and regenerative medicine to promote endogenous tissue regeneration. Here, we developed a 3D human in vitro model mimicking the signature of pathological tendon and used it to evaluate the influence that different platelet-derived EVs might have in tendon tissue repair mechanisms. For this, different EV populations isolated from platelets, small EVs (sEVs) and medium EVs (mEVs), were added to the culture media of human tendon-derived cells (hTDCs) cultured on isotropic nanofibrous scaffolds. The platelet-derived EVs increased the expression of tenogenic markers, promoted a healthy extracellular matrix (ECM) remodeling, and the synthesis of anti-inflammatory mediators. These findings suggest that platelet EVs provided relevant biochemical cues that potentiated a recovery of hTDCs phenotype from a diseased to a healthy state. Thus, this study opens new perspectives for the translation of platelet-derived EVs as therapeutics.

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Section: Resultsmentioning

confidence: 99%

Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model

Graça

Domingues

Calejo

et al. 2022

IJMS

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“…Nonetheless, as research in tendinopathy pathophysiology has firmly identified a chronic degeneration of the matrix microenvironment, it is now increasingly evident that inflammatory responses are continuously activated within the tendon matrix microenvironment during tissue injury and contribute to dysregulated homeostasis ( Millar et al, 2017 ). However, advancements in cellular profiling using genetic and molecular tools enabled research demonstrating the presence of mast cells, granulocytes, macrophages, T cells, and B cells in both acute and chronic human tendinopathic tissues ( Arvind and Huang 2021 ). In this study, we identified p-sites of proteins involved in neutrophil reaction that were upregulated.…”

Section: Discussionmentioning

confidence: 99%

A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy

Wang

Zhang

Lin

et al. 2022

Front. Mol. Biosci.

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Rotator cuff tendinopathy (RCT) is the most common cause of shoulder pain, therefore posing an important clinical problem. Understanding the mechanism and biochemical changes of RCT would be of crucial importance and pave the path to targeting novel and effective therapeutic strategies in translational perspectives and clinical practices. Phosphorylation, as one of the most important and well-studied post-translational modifications, is tightly associated with protein activity and protein functional regulation. Here in this study, we generated a global protein phosphorylation atlas within the pathological site of human RCT patients. By using Tandem Mass Tag (TMT) labeling combined with mass spectrometry, an average of 7,741 phosphorylation sites (p-sites) and 3,026 proteins were identified. Compared with their normal counterparts, 1,668 p-sites in 706 proteins were identified as upregulated, while 73 p-sites in 57 proteins were downregulated. GO enrichment analyses have shown that majority of proteins with upregulated p-sites functioned in neutrophil-mediated immunity whereas downregulated p-sites are mainly involved in muscle development. Furthermore, pathway analysis identified NF-κB–related TNF signaling pathway and protein kinase C alpha type (PKCα)–related Wnt signaling pathway were associated with RCT pathology. At last, a weighted kinase-site phosphorylation network was built to identify potentially core kinase, from which serine/threonine-protein kinase 39 (STLK3) and mammalian STE20-like protein kinase 1 (MST1) were proposed to be positively correlated with the activation of Wnt pathway.

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“…The recruited cells start to secrete pro-inflammatory cytokines and chemokines, hence increasing the immune cell recruitment and promoting inflammation ( Figure 3 C) [ 32 ]. Afterwards, immune cells from the adaptive immune response including B cells, CD4+ and CD8+ T cells, natural killer (NK) cells, and innate lymphoid cells start to release cytokines and chemokines within the implanted site [ 32 , 79 , 80 , 81 ]. The occurrence of acute and chronic inflammation is followed by the formation of neovascularized connective tissue, called granulation tissue.…”

Section: Immune Response Induced By Scaffold Implantationmentioning

confidence: 99%

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Russo

Khatib

Prencipe

et al. 2022

Cells

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Tendon injuries are at the frontier of innovative approaches to public health concerns and sectoral policy objectives. Indeed, these injuries remain difficult to manage due to tendon’s poor healing ability ascribable to a hypo-cellularity and low vascularity, leading to the formation of a fibrotic tissue affecting its functionality. Tissue engineering represents a promising solution for the regeneration of damaged tendons with the aim to stimulate tissue regeneration or to produce functional implantable biomaterials. However, any technological advancement must take into consideration the role of the immune system in tissue regeneration and the potential of biomaterial scaffolds to control the immune signaling, creating a pro-regenerative environment. In this context, immunoengineering has emerged as a new discipline, developing innovative strategies for tendon injuries. It aims at designing scaffolds, in combination with engineered bioactive molecules and/or stem cells, able to modulate the interaction between the transplanted biomaterial-scaffold and the host tissue allowing a pro-regenerative immune response, therefore hindering fibrosis occurrence at the injury site and guiding tendon regeneration. Thus, this review is aimed at giving an overview on the role exerted from different tissue engineering actors in leading immunoregeneration by crosstalking with stem and immune cells to generate new paradigms in designing regenerative medicine approaches for tendon injuries.

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Reparative and Maladaptive Inflammation in Tendon Healing

Cited by 61 publications

References 189 publications

Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model

Therapeutic Effects of Platelet-Derived Extracellular Vesicles in a Bioengineered Tendon Disease Model

A Global Phosphorylation Atlas of Proteins Within Pathological Site of Rotator Cuff Tendinopathy

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

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