Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation

Feng, Yi; Sun, Ziyong; Liu, Siyu; Wu, Junjie; Zhao, Bin-Hong; Lv, Guozhong; Du, Yong; Yu, Sheng; Yang, Ming-Lie; Yuan, Feng‐Lai; Zhou, Xianghui

doi:10.3389/fphys.2019.01101

Cited by 50 publications

(42 citation statements)

References 67 publications

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“…Particular studies suggest that AMSCs may be superior in promoting an M1 to M2 phenotype transition in macrophages that favour resolution of inflammation (Heo et al 2019). This is relevant as macrophages are a key mediator of the pathogenic process of excessive scarring (Feng et al 2019;Hesketh et al 2017). In addition, certain MSCs demonstrate a greater ability to engraft onto lesions and can therefore produce more sustained effects (Burk et al 2016).…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell therapy in hypertrophic and keloid scars

Bojanic

Hatoum

et al. 2021

Cell Tissue Res

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Scars are the normal outcome of wound repair and involve a co-ordinated inflammatory and fibrotic process. When a scar does not resolve, uncontrolled chronic inflammation can persist and elicits excessive scarring that leads to a range of abnormal phenotypes such as hypertrophic and keloid scars. These pathologies result in significant impairment of quality of life over a long period of time. Existing treatment options are generally unsatisfactory, and there is mounting interest in innovative cell-based therapies. Despite the interest in mesenchymal stem cells (MSCs), there is yet to be a human clinical trial that investigates the potential of MSCs in treating abnormal scarring. A synthesis of existing evidence of animal studies may therefore provide insight into the barriers to human application. The aim of this PRISMA systematic review was to evaluate the effectiveness of MSC transplantation in the treatment of hypertrophic and keloid scars in in vivo models. A total of 11 case-control studies were identified that treated a total of 156 subjects with MSCs or MSC-conditioned media. Ten studies assessed hypertrophic scars, and one looked at keloid scars. All studies evaluated scars in terms of macroscopic and histological appearances and most incorporated immunohistochemistry. The included studies all found improvements in the above outcomes with MSC or MSC-conditioned media without complications. The studies reviewed support a role for MSC therapy in treating scars that needs further exploration. The transferability of these findings to humans is limited by factors such as the reliability and validity of the disease model, the need to identify the optimal MSC cell source, and the outcome measures employed.

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Section: Discussionmentioning

confidence: 99%

Mesenchymal stem cell therapy in hypertrophic and keloid scars

Bojanic

Hatoum

et al. 2021

Cell Tissue Res

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“…M2-like macrophages participate in the resolution of inflammation by playing direct and indirect roles in tissue healing and remodeling. They produce different components of the extracellular matrix (ECM), such as types I and III collagen and matrix metallopeptidases (MMPs) ( Feng et al, 2019 ), or transition into collagen-producing fibroblasts through a macrophage-myofibroblast transition process regulated by TGF-β ( Wang et al, 2016 ). M2-like macrophages can also secrete proangiogenic factors such as vascular endothelial growth factor or platelet-derived growth factor to promote vascularization of the healed tissues ( Braga et al, 2015 ).…”

Section: The Role Of Macrophage Phenotypes During Viral Infectionsmentioning

confidence: 99%

“…M2-like macrophages can also secrete proangiogenic factors such as vascular endothelial growth factor or platelet-derived growth factor to promote vascularization of the healed tissues ( Braga et al, 2015 ). Indirect roles include stimulating fibroblasts through TGF-β ( Braga et al, 2015 ; Sheng et al, 2018 ) to promote ECM deposition, wound healing, and scar formation ( Feng et al, 2019 ).…”

Section: The Role Of Macrophage Phenotypes During Viral Infectionsmentioning

confidence: 99%

“…Despite their differences, M1-and M2-like macrophages share some characteristics. For example, M1-like are also associated with wound healing properties by secretion of MMPs and CCL2 ( Braga et al, 2015 ; Feng et al, 2019 ). The latter can recruit fibrocytes that differentiate into fibroblasts to help with ECM deposition.…”

Section: The Role Of Macrophage Phenotypes During Viral Infectionsmentioning

confidence: 99%

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Targeting Macrophages as a Therapeutic Option in Coronavirus Disease 2019

2020

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Immune cells of the monocyte/macrophage lineage are characterized by their diversity, plasticity, and variety of functions. Among them, macrophages play a central role in antiviral responses, tissue repair, and fibrosis. Macrophages can be reprogrammed by environmental cues, thus changing their phenotype during an antiviral immune response as the viral infection progresses. While M1-like macrophages are essential for the initial inflammatory responses, M2-like macrophages are critical for tissue repair after pathogen clearance. Numerous reports have evaluated the detrimental effects that coronaviruses, e.g., HCoV-229E, SARS-CoV, MERS-CoV, and SARS-CoV-2, have on the antiviral immune response and macrophage functions. In this review, we have addressed the breadth of macrophage phenotypes during the antiviral response and provided an overview of macrophage-coronavirus interactions. We also discussed therapeutic approaches to target macrophage-induced complications, currently under evaluation in clinical trials for coronavirus disease 2019 patients. Additionally, we have proposed alternative approaches that target macrophage recruitment, interferon signaling, cytokine storm, pulmonary fibrosis, and hypercoagulability.

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“…Известно, что Мφ принимают активное участие в регуляции пролиферации и дифференцировки фибробластов, образовании и деградации ВКМ, тем самым способствуя или препятствуя фибротическому процессу [1,25]. При этом действие Мφ может быть прямым или опосредованным растворимыми факторами [6], среди которых наибольший интерес представляют факторы роста и плейотропные цитокины (IL-10, TNFα, IL-4, IL-6, IFNγ и др. ), регулирующие активность фибробластов и миофибробластов, а также синтез и продукцию коллагена и других белков ВКМ.…”

Section: Introductionunclassified

Production of factors involved into fibrosis regulation by various types of human macrophages

Максимова¹,

Shevela²,

Сахно³

et al. 2020

Med. immunol.

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Macrophages (Mφ) play a key role in regulation of fibrogenesis, including proliferation of fibroblasts and myofibroblasts, differentiation of progenitor cells into myofibroblasts, as well as synthesis and secretion of the extracellular matrix, mainly collagen. The direction of the Mφ effects (stimulation or suppression) is determined by a number of factors, including the stage of the fibrotic process and the Mφ functional phenotype dependent on the signals of microenvironment. One of the feasible ways of the fibrogenesis regulating is the secretion of pro-or antifibrotic factors such as matrix metalloproteinases, inhibitors of metalloproteinases and some cytokines. However, existing data on ability to secrete these factors by various subpopulations of human Mφ are rare and controversial. The aim of this study was to characterize the ability of human M1, M2a, and M2c Mφ differentiating in the presence of GM-CSF to produce matrix metalloproteinases (MMP-9) and their tissue inhibitors (TIMP-1), as well as some cytokines and growth factors. As compared to M2 macrophages, the M1 macrophages polarized by lipopolysaccharide produced significantly more TNFα, IL-6 and IL-2 that have pro-inflammatory activity and are able to initiate a fibrotic process. In turn, M2a Mφ stimulated by IL-4 were characterized by a high level of VEGF production and, at the same time, low levels of TNFα and IL-6, which may determine the important role of these cells at the proliferative stage of fibrosis and stimulation of extracellular matrix deposition. Finally, M2c Mφ polarized by dexamethasone, exhibited the М2а-like cytokine profile, i.e., VEGF was actively produced against the background of low TNFα and IL-6 synthesis. Moreover, all three Mφ subpopulations did actively secrete MMP-9 and TIMP-1, without significant difference in production of these factors. However, M2c Mφ differed by a significantly higher MMP-9/TIMP-1 ratio index compared to M1 and M2a Mφ, and it is crucial at the rearrangement stage of the fibrotic process. Thus, the production of MMP-9 and TIMP-1, together with other pleiotropic cytokines and growth factors by various Mφ subtypes may reflect their role in regulation of fibrotic process at various stages.

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Direct and Indirect Roles of Macrophages in Hypertrophic Scar Formation

Cited by 50 publications

References 67 publications

Mesenchymal stem cell therapy in hypertrophic and keloid scars

Mesenchymal stem cell therapy in hypertrophic and keloid scars

Targeting Macrophages as a Therapeutic Option in Coronavirus Disease 2019

Production of factors involved into fibrosis regulation by various types of human macrophages

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