Tissue-specific contribution of macrophages to wound healing
TL;DR: This review evaluates how macrophages in two fundamentally distinct tissues, i.e. the lung and the skin, differentially contribute to the process of wound healing.
About: This article is published in Seminars in Cell & Developmental Biology.The article was published on 2017-01-01 and is currently open access. It has received 327 citations till now. The article focuses on the topics: Wound healing & Skin repair.
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TL;DR: The physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models are discussed.
Abstract: Macrophages play key roles in all phases of adult wound healing, which are inflammation, proliferation, and remodeling. As wounds heal, the local macrophage population transitions from predominantly pro-inflammatory (M1-like phenotypes) to anti-inflammatory (M2-like phenotypes). Non-healing chronic wounds, such as pressure, arterial, venous, and diabetic ulcers indefinitely remain in inflammation-the first stage of wound healing. Thus, local macrophages retain pro-inflammatory characteristics. This review discusses the physiology of monocytes and macrophages in acute wound healing and the different phenotypes described in the literature for both in vitro and in vivo models. We also discuss aberrations that occur in macrophage populations in chronic wounds, and attempts to restore macrophage function by therapeutic approaches. These include endogenous M1 attenuation, exogenous M2 supplementation and endogenous macrophage modulation/M2 promotion via mesenchymal stem cells, growth factors, biomaterials, heme oxygenase-1 (HO-1) expression, and oxygen therapy. We recognize the challenges and controversies that exist in this field, such as standardization of macrophage phenotype nomenclature, definition of their distinct roles and understanding which phenotype is optimal in order to promote healing in chronic wounds.
754 citations
TL;DR: The mechanisms by which type 2 immunity contributes to tissue regeneration and fibrosis following injury are discussed.
Abstract: Type 2 immunity is characterized by the production of IL-4, IL-5, IL-9 and IL-13, and this immune response is commonly observed in tissues during allergic inflammation or infection with helminth parasites. However, many of the key cell types associated with type 2 immune responses - including T helper 2 cells, eosinophils, mast cells, basophils, type 2 innate lymphoid cells and IL-4- and IL-13-activated macrophages - also regulate tissue repair following injury. Indeed, these cell populations engage in crucial protective activity by reducing tissue inflammation and activating important tissue-regenerative mechanisms. Nevertheless, when type 2 cytokine-mediated repair processes become chronic, over-exuberant or dysregulated, they can also contribute to the development of pathological fibrosis in many different organ systems. In this Review, we discuss the mechanisms by which type 2 immunity contributes to tissue regeneration and fibrosis following injury.
593 citations
TL;DR: The unique biological properties of a chitosan-based hydrogel enable it to serve as both a wound dressing and as a drug delivery system (DDS) to deliver antibacterial agents, growth factors, stem cells and so on, which could further accelerate wound healing.
Abstract: Functional active wound dressings are expected to provide a moist wound environment, offer protection from secondary infections, remove wound exudate and accelerate tissue regeneration, as well as to improve the efficiency of wound healing. Chitosan-based hydrogels are considered as ideal materials for enhancing wound healing owing to their biodegradable, biocompatible, non-toxic, antimicrobial, biologically adhesive, biological activity and hemostatic effects. Chitosan-based hydrogels have been demonstrated to promote wound healing at different wound healing stages, and also can alleviate the factors against wound healing (such as excessive inflammatory and chronic wound infection). The unique biological properties of a chitosan-based hydrogel enable it to serve as both a wound dressing and as a drug delivery system (DDS) to deliver antibacterial agents, growth factors, stem cells and so on, which could further accelerate wound healing. For various kinds of wounds, chitosan-based hydrogels are able to promote the effectiveness of wound healing by modifying or combining with other polymers, and carrying different types of active substances. In this review, we will take a close look at the application of chitosan-based hydrogels in wound dressings and DDS to enhance wound healing.
452 citations
TL;DR: The current understanding of the core functions of TGF-β1 in promoting collagen accumulation, parallel pathways that promote physiological repair, and pathological triggers that tip the balance toward progressive fibrosis are examined.
Abstract: Activation of TGF-β1 initiates a program of temporary collagen accumulation important to wound repair in many organs. However, the outcome of temporary extracellular matrix strengthening all too frequently morphs into progressive fibrosis, contributing to morbidity and mortality worldwide. To avoid this maladaptive outcome, TGF-β1 signaling is regulated at numerous levels and intimately connected to feedback signals that limit accumulation. Here, we examine the current understanding of the core functions of TGF-β1 in promoting collagen accumulation, parallel pathways that promote physiological repair, and pathological triggers that tip the balance toward progressive fibrosis. Implicit in better understanding of these processes is the identification of therapeutic opportunities that will need to be further advanced to limit or reverse organ fibrosis.
360 citations
Cites background from "Tissue-specific contribution of mac..."
...Inflammatory cells, especially macrophages, are important initiators of inflammation and mediators of inflammation resolution (Vannella and Wynn 2016; Minutti et al. 2017)....
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TL;DR: This review covers comprehensively the advanced treatment strategies to improve the quality of wound healing and includes growth factor and gene delivery as well as cell therapy.
308 citations
References
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TL;DR: Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
Abstract: The healing of an adult skin wound is a complex process requiring the collaborative efforts of many different tissues and cell lineages. The behavior of each of the contributing cell types during the phases of proliferation, migration, matrix synthesis, and contraction, as well as the growth factor and matrix signals present at a wound site, are now roughly understood. Details of how these signals control wound cell activities are beginning to emerge, and studies of healing in embryos have begun to show how the normal adult repair process might be readjusted to make it less like patching up and more like regeneration.
4,558 citations
"Tissue-specific contribution of mac..." refers background in this paper
...These phases have been defined as “coagulation and inflammation”, “tissue formation” and “tissue remodeling” [1]....
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...It consists of platelets that are embedded in cross-linked fibrin fibers derived by thrombin cleavage of fibrinogen [1]....
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...In particular the sustained and sometimes excessive influx and activation of neutrophils into the wound is detrimental for the wound healing process [1]....
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St. Jude Children's Research Hospital1, University of Edinburgh2, Singapore Immunology Network3, New York University4, University College London5, Heidelberg University6, University of Oxford7, Royal Melbourne Hospital8, Hospital for Special Surgery9, University of Milan10, Aix-Marseille University11, University of Maryland, College Park12, European Institute of Oncology13, Massachusetts Institute of Technology14, University of Bonn15, University of Maryland, Baltimore16, University of Eastern Piedmont17, University of Louisville18, Vrije Universiteit Brussel19, National Institutes of Health20
TL;DR: A set of standards encompassing three principles-the source of macrophages, definition of the activators, and a consensus collection of markers to describe macrophage activation are described with the goal of unifying experimental standards for diverse experimental scenarios.
4,287 citations
TL;DR: Using a murine adoptive transfer system to probe monocyte homing and differentiation in vivo, two functional subsets among murine blood monocytes are identified: a short-lived CX(3)CR1(lo)CCR2(+)Gr1(+) subset that is actively recruited to inflamed tissues and a CX (3) CR1(hi)CCS1-dependent recruitment to noninflamed tissues.
3,307 citations
TL;DR: This review discusses the mechanisms that instruct macrophages to adopt pro-inflammatory, pro-wound-healing,pro-fibrotic, anti- inflammatory, anti -fib rotic, Pro-resolving, and tissue-regenerating phenotypes after injury, and highlights how some of these mechanisms and macrophage activation states could be exploited therapeutically.
2,284 citations
TL;DR: This review focuses on the healing processes of the skin and highlights the classical wound healing phases and the physiological endpoint of mammalian wound repair displays the formation of a scar, which is directly linked to the extent of the inflammatory process throughout wound healing.
Abstract: The skin is the biggest organ of the human being and has many functions. Therefore, the healing of a skin wound displays an extraordinary mechanism of cascading cellular functions which is unique in nature. As healing and regeneration processes take place in all parts of the human body, this review focuses on the healing processes of the skin and highlights the classical wound healing phases. While regeneration describes the specific substitution of the tissue, i.e. the superficial epidermis, mucosa or fetal skin, skin repair displays an unspecific form of healing in which the wound heals by fibrosis and scar formation. The first stage of acute wound healing is dedicated to hemostasis and the formation of a provisional wound matrix, which occurs immediately after injury and is completed after some hours. Furthermore, this phase initiates the inflammatory process. The inflammatory phase of the wound healing cascade gets activated during the coagulation phase and can roughly be divided into an early phase with neutrophil recruitment and a late phase with the appearance and transformation of monocytes. In the phase of proliferation the main focus of the healing process lies in the recovering of the wound surface, the formation of granulation tissue and the restoration of the vascular network. Therefore, next to the immigration of local fibroblasts along the fibrin network and the beginning of reepithelialization from the wound edges, neovascularization and angiogenesis get activated by capillary sprouting. The formation of granulation tissue stops through apoptosis of the cells, characterizing a mature wound as avascular as well as acellular. During the maturation of the wound the components of the extracellular matrix undergo certain changes. The physiological endpoint of mammalian wound repair displays the formation of a scar, which is directly linked to the extent of the inflammatory process throughout wound healing.
2,242 citations
"Tissue-specific contribution of mac..." refers background in this paper
...During this phase of wound healing, macrophages contribute to wound healing by ingesting cell debris and contributing to the degradation of excess ECM that had built up in and around the wound [88]....
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