Exosome-educated macrophages and exosomes differentially improve ligament healing

Chamberlain, Connie S.; Kink, John A.; Wildenauer, Linzie A.; McCaughey, Maxwell; Henry, Katie; Spiker, Andrea M.; Halanski, Matthew A.; Hematti, Peiman; Vanderby, Ray

doi:10.1002/stem.3291

Cited by 45 publications

(30 citation statements)

References 25 publications

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“…Furthermore, compared with untreated mice, Exo-PEF promoted the secretion of IL-4, IL-10, and IL-13 and decreased the pro-inflammatory chemokines TNF-α and IFN-γ [ 156 ]. Another example of exosome involvement was shown by Chamberlain et al, which generated M2-like macrophages, avoiding the usage of MSCs directly, by using exosomes isolated from MSCs and creating exosome-educated macrophages (EEMs) [ 182 , 183 ]. For example, the researchers next compared the effects of EEMs on mouse Achilles’ tendon rupture to normal tendon healing, MSCs, and EVs.…”

Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

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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Section: Scaffold Immunoengineering Strategies For Tendon Te Applicationsmentioning

confidence: 99%

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Russo

Khatib

Prencipe

et al. 2022

Cells

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“…However, the role of DSF on macrophage is unknown. In TI, the functional phenotype change of M1 and M2 exhibits a phagocytic and pro-inflammatory function, which plays an important role in the healing process ( Chamberlain et al, 2021 ; Yu et al, 2021 ). Furthermore, the reduced macrophage-mediated inflammation in the injured tendon through M1-to-M2 transmission significantly inhibits adhesion formation during tendon healing ( Dong et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Disulfiram Suppressed Peritendinous Fibrosis Through Inhibiting Macrophage Accumulation and Its Pro-inflammatory Properties in Tendon Bone Healing

Zhou

Wang

Yang

et al. 2022

Front. Bioeng. Biotechnol.

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The communication between macrophages and tendon cells plays a critical role in regulating the tendon-healing process. However, the potential mechanisms through which macrophages can control peritendinous fibrosis are unknown. Our data showed a strong pro-inflammatory phenotype of macrophages after a mouse tendon–bone injury. Moreover, by using a small-molecule compound library, we identified an aldehyde dehydrogenase inhibitor, disulfiram (DSF), which can significantly promote the transition of macrophage from M1 to M2 phenotype and decrease macrophage pro-inflammatory phenotype. Mechanistically, DSF targets gasdermin D (GSDMD) to attenuate macrophage cell pyroptosis, interleukin-1β, and high mobility group box 1 protein release. These pro-inflammatory cytokines and damage-associated molecular patterns are essential for regulating tenocyte and fibroblast proliferation, migration, and fibrotic activity. Deficiency or inhibition of GSDMD significantly suppressed peritendinous fibrosis formation around the injured tendon and was accompanied by increased regenerated bone and fibrocartilage compared with the wild-type littermates. Collectively, these findings reveal a novel pathway of GSDMD-dependent macrophage cell pyroptosis in remodeling fibrogenesis in tendon–bone injury. Thus, GSDMD may represent a potential therapeutic target in tendon–bone healing.

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“…These EEMs showed an acceleration in ligament ligation and reduced inflammation in the rat medial collateral ligament (MCL) injury model. 29 …”

Section: Innate Immune Cells and Osteoporosismentioning

confidence: 99%

The Rising Era of “Immunoporosis”: Role of Immune System in the Pathophysiology of Osteoporosis

Srivastava¹,

Sapra²

2022

JIR

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Discoveries in the last few years have emphasized the existence of an enormous breadth of communication between bone and the immune system in maintaining skeletal homeostasis. Originally, the discovery of various factors was assigned to the immune system viz. interleukin (IL)-6, IL-10, IL-17, tumor necrosis factor (TNF)-α, receptor activator of nuclear factor kappa B ligand (RANKL), nuclear factor of activated T cells (NFATc1), etc., but now these factors have also been shown to have a significant impact on osteoblasts (OBs) and osteoclasts (OCs) biology. These discoveries led to an alteration in the approach for the treatment of several bone pathologies including osteoporosis. Osteoporosis is an inflammatory bone anomaly affecting more than 500 million people globally. In 2018, to highlight the importance of the immune system in the pathophysiology of osteoporosis, our group coined the term “immunoporosis”. In the present review, we exhaustively revisit the characteristics, mechanism of action, and function of both innate and adaptive immune cells with the goal of understanding the potential of immune cells in osteoporosis. We also highlight the Immunoporotic role of gut microbiota (GM) for the treatment and management of osteoporosis. Importantly, we further discuss whether an immune cell-based strategy to treat and manage osteoporosis is feasible and relevant in clinical settings.

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Exosome-educated macrophages and exosomes differentially improve ligament healing

Cited by 45 publications

References 25 publications

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Scaffold-Mediated Immunoengineering as Innovative Strategy for Tendon Regeneration

Disulfiram Suppressed Peritendinous Fibrosis Through Inhibiting Macrophage Accumulation and Its Pro-inflammatory Properties in Tendon Bone Healing

The Rising Era of “Immunoporosis”: Role of Immune System in the Pathophysiology of Osteoporosis

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