Promoting tissue regeneration by modulating the immune system

Julier, Ziad; Park, Anthony; Briquez, Priscilla S.; Martino, Mikaël M.

doi:10.1016/j.actbio.2017.01.056

Cited by 539 publications

(443 citation statements)

References 209 publications

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“…In the first days after injury, M1 (CD68 + ) macrophages predominate probably due to stimuli received from the IFN‐γ and TNF‐α enriched environment 1. CD206 + macrophages peak on Day 4 after a muscle injury4 and these cells mainly express TGFβ, arginase, chemokine motif ligand 18 (CCL18), VEGF‐A, platelet‐derived growth factor (PDGF) and insulin‐like growth factor (IGF) as well as other growth factors, which favours tissue repair 1, 25, 26. CD206 expression can be increased by IL‐4, the granulocyte macrophage colony‐stimulating factor (GM‐CSF) and TGF‐β 1, 25, 26.…”

Section: Discussionmentioning

confidence: 99%

Photobiomodulation and different macrophages phenotypes during muscle tissue repair

Souza

Mesquita‐Ferrari

Rodrigues

et al. 2018

J Cellular Molecular Medi

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Macrophages play a very important role in the conduction of several regenerative processes mainly due to their plasticity and multiple functions. In the muscle repair process, while M1 macrophages regulate the inflammatory and proliferative phases, M2 (anti‐inflammatory) macrophages direct the differentiation and remodelling phases, leading to tissue regeneration. The aim of this study was to evaluate the effect of red and near infrared (NIR) photobiomodulation (PBM) on macrophage phenotypes and correlate these findings with the repair process following acute muscle injury. Wistar rats were divided into 4 groups: control; muscle injury; muscle injury + red PBM; and muscle injury + NIR PBM. After 2, 4 and 7 days, the tibialis anterior muscle was processed for analysis. Macrophages phenotypic profile was evaluated by immunohistochemistry and correlated with the different stages of the skeletal muscle repair by the qualitative and quantitative morphological analysis as well as by the evaluation of IL‐6,TNF‐α and TGF‐β mRNA expression. Photobiomodulation at both wavelengths was able to decrease the number of CD68+ (M1) macrophages 2 days after muscle injury and increase the number of CD163+ (M2) macrophages 7 days after injury. However, only NIR treatment was able to increase the number of CD206+ M2 macrophages (Day 2) and TGF ‐β mRNA expression (Day 2, 4 and 7), favouring the repair process more expressivelly. Treatment with PBM was able to modulate the inflammation phase, optimize the transition from the inflammatory to the regeneration phase (mainly with NIR light) and improve the final step of regeneration, enhancing tissue repair.

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Section: Discussionmentioning

confidence: 99%

Photobiomodulation and different macrophages phenotypes during muscle tissue repair

Souza

Mesquita‐Ferrari

Rodrigues

et al. 2018

J Cellular Molecular Medi

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“…The immune cells, infiltrating into the fracture gap, secrete factors that stimulate migration, proliferation and differentiation of osteoprogenitor cells [3,4,5]. Thus, the immune system plays a central role in tissue repair and regeneration, as it determines speed and outcome of the healing process [29]. Indeed, patients with both an over-activated and a suppressed immune systems frequently show delayed fracture healing [30].…”

Section: Discussionmentioning

confidence: 99%

Immune Cell Induced Migration of Osteoprogenitor Cells Is Mediated by TGF-β Dependent Upregulation of NOX4 and Activation of Focal Adhesion Kinase

Ehnert¹,

Aspera-Werz²,

Bykova³

et al. 2018

IJMS

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The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-β), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and focal adhesion kinase (FAK) as possible regulators. Monocyte- and macrophage (THP-1 cells ± phorbol 12-myristate 13-acetate (PMA) treatment)-conditioned media, other than the granulocyte-conditioned medium (HL-60 cells + dimethyl sulfoxide (DMSO) treatment), induce migration of phOBs. Monocyte- and macrophage (THP-1 cells)-conditioned media activate Smad3-dependent TGF-β signaling in the phOBs. Stimulation with TGF-β promotes migration of phOBs. Furthermore, TGF-β treatment strongly induces NOX4 expression on both mRNA and protein levels. The associated reactive oxygen species (ROS) accumulation results in phosphorylation (Y397) of FAK. Blocking TGF-β signaling, NOX4 activity and FAK signaling effectively inhibits the migration of phOBs towards TGF-β. In summary, our data suggest that monocytic- and macrophage-like cells induce migration of phOBs in a TGF-β-dependent manner, with TGF-β-dependent induction of NOX4, associated production of ROS and resulting activation of FAK as key mediators.

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“…14–21 Characterization of the T cell response to polypropylene prolapse mesh and the role of T cells in complications, however, remains unclear. The purpose of this study was twofold: 1) to define and characterize the fibrotic capsule in polypropylene mesh tissue complexes removed for the separate complications of pain versus mesh exposure and 2) to compare the T cell response in patients with pain – a presumably fibrotic response vs exposure – a response purportedly associated with degradation.…”

Section: Introductionmentioning

confidence: 99%

Characterization of the T-cell response to polypropylene mesh in women with complications

Tennyson

Rytel

Palcsey

et al. 2019

American Journal of Obstetrics and Gynecology

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Background: Polypropylene mesh is widely used for surgical treatment of pelvic organ prolapse and stress urinary incontinence. While these surgeries demonstrate favorable functional and anatomical outcomes, their use has been limited by complications, the two most common being exposure and pain. Growing evidence suggests T lymphocytes play a critical role in regulating the host response to biomaterials. Objectives: To define and characterize the T cell response and correlate the response to collagen deposition in fibrotic capsules in mesh tissue complexes removed for the complications of pain versus exposure. Study Design: Patients who were scheduled to undergo a surgical excision of mesh for pain or exposure at Magee-Women’s Hospital were offered enrollment. Forty- two mesh-vagina tissue complexes were removed for the primary complaint of exposure (n=24) versus pain (n=18). Twenty-one patients agreed to have an additional vaginal biopsy away from the site of mesh and served as control tissue. T cells were examined via immunofluorescent labeling for cell surface markers CD4+ (T helper), CD8+ (cytotoxic) and foxp3 (T regulatory cell). Frozen sections were stained with H&E for gross morphology and picrosirius red for collagen fiber analysis. Interrupted sodium-dodecyl sulfate gel electrophoresis was used to quantify the content of collagens type I and III, and the collagen III/I ratio. Growth factors TGF-β and CTGF implicated in the development of fibrosis were measured via enzyme-linked immunosorbent assays. Data were analyzed using Student’s t-tests, mixed effects linear regression, and Spearman’s correlation coefficients. Results: Demographic data were not different between groups except for BMI, which was 31.7 for the exposure group and 28.2 for pain (P=0.04). Tissue complexes demonstrated a marked, but highly localized foreign body response. We consistently observed a teardrop shaped fibroma encapsulating mesh fibers in both pain and exposure groups, with the T cells localized within the tip of this configuration away from the mesh-tissue interface. All three T cell populations were significantly increased relative to control - CD4+ Thelper (P<0.001), foxp3+ Treg (P<0.001) and CD8+ cytotoxic T cell (P=0.034) in the exposure group. In the pain group, only Thelper (P<0.001) and Treg cells (P<0.001) were increased, with cytotoxic T cells (P=0.520) not different from control. Picrosirius red staining showed a greater area of green (thin) fibers in the exposure group (P=0.025) and red (thick) fibers in the pain group (P<0.001). The ratio of area green/(yellow + orange + red) representing thin vs. thick fibers was significantly greater in the exposure group (P=0.005). Analysis of collagen showed that collagen type I was increased by 35% in samples with mesh complications (exposure and pain) when compared to controls (P=0.043). Strong correlations between the pro-fibrosis cytokine TGF-β and collagen type I and III were found in patients with pain (r≥0.833; P=0.01) but not exposure (P>0.7). Conclusion: T cell...

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Promoting tissue regeneration by modulating the immune system

Cited by 539 publications

References 209 publications

Photobiomodulation and different macrophages phenotypes during muscle tissue repair

Photobiomodulation and different macrophages phenotypes during muscle tissue repair

Immune Cell Induced Migration of Osteoprogenitor Cells Is Mediated by TGF-β Dependent Upregulation of NOX4 and Activation of Focal Adhesion Kinase

Characterization of the T-cell response to polypropylene mesh in women with complications

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