Targeting the myofibroblast to improve wound healing

Hinz, Boris

doi:10.1016/b978-1-78242-455-0.00003-3

Cited by 6 publications

(5 citation statements)

References 247 publications

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“…Side effects are also a main limitation for therapies that target TGF-β1 or TGF-β1 receptor components, due to the pleiotropic character of the growth factor. More recent strategies tackle different components of the TGF-β1 activation machinery, which provide cell-and context-specificity (Akhurst, 2017;de Gramont et al, 2017;Friedman et al, 2013;Ganesh and Massague, 2018;Hinz, 2016c;Huynh et al, 2019;Lodyga and Hinz, 2019;Varga and Pasche, 2009). However, broader drug actions may also be beneficial, as in the case of the two only licensed antifibrotic drugs Nintedanib and Pirfenidone, of which Nintedanib targets multiple kinases involved in key profibrotic signaling pathways (Richeldi et al, 2014;Sun et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

The myofibroblast at a glance

Pakshir

Noskovičová

Lodyga

et al. 2020

Journal of Cell Science

189

169

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In 1971, Gabbiani and co-workers discovered and characterized the “modification of fibroblasts into cells which are capable of an active spasm” (contraction) in rat wound granulation tissue and, accordingly, named these cells ‘myofibroblasts’. Now, myofibroblasts are not only recognized for their physiological role in tissue repair but also as cells that are key in promoting the development of fibrosis in all organs. In this Cell Science at a Glance and the accompanying poster, we provide an overview of the current understanding of central aspects of myofibroblast biology, such as their definition, activation from different precursors, the involved signaling pathways and most widely used models to study their function. Myofibroblasts will be placed into context with their extracellular matrix and with other cell types communicating in the fibrotic environment. Furthermore, the challenges and strategies to target myofibroblasts in anti-fibrotic therapies are summarized to emphasize their crucial role in disease progression.

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Section: Discussionmentioning

confidence: 99%

The myofibroblast at a glance

Pakshir

Noskovičová

Lodyga

et al. 2020

Journal of Cell Science

189

169

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“…So far, we have mainly discussed strategies that aim at eliminating or inhibiting myofibroblast functions in skin hypertrophic scarring and organ fibrosis. Here, we will briefly consider the consequences of myofibroblast depletion for the normal tissue repair process and how mechanical stimulation can be used in clinical practice to reestablish missing or dysfunctional granulation tissue in the context of nonhealing, chronic wounds (Hinz 2016b;Lebonvallet et al 2018;desJardins-Park et al 2021). The prevalence of nonhealing chronic wounds increases with ongoing age and in the presence of risk factors such as diabetes and vasculopathies (des-Jardins-Park et al 2021).…”

Section: Mechanical Stimulation Of Myofibroblasts To Improve Healing ...mentioning

confidence: 99%

“…The prevalence of nonhealing chronic wounds increases with ongoing age and in the presence of risk factors such as diabetes and vasculopathies (des-Jardins-Park et al 2021). Infections, exacerbated inflammation, ischemia, hypoxia, and hyperglycemia characteristic for chronic wound beds all repress the formation of myofibroblasts and vascularization, resulting in an overall poorly developed granulation tissue (Hinz 2016b;Bonte et al 2019;Wan et al 2021;Yokota et al 2021). Tissue hypoxia resulting from poor vascularization inhibits fibroblast proliferation and formation of reparative collagen ECM; several crucial events in collagen fiber assembly and cross-linking depend on adequate oxygen concentrations (Scheid et al 2000).…”

Section: Mechanical Stimulation Of Myofibroblasts To Improve Healing ...mentioning

confidence: 99%

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The Role of Myofibroblasts in Physiological and Pathological Tissue Repair

Schuster

Younesi

Ezzo

et al. 2022

Cold Spring Harb Perspect Biol

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“…Other studies targeted collagen type I synthesis using small interfering RNA which resulted in significant decrease the fibrous capsule thickness in a mouse implant model [ 195 ] ( Table 1 ). We and others have already amply reviewed current strategies and therapies to counteract fibrosis in different organs [ 56 , 190 , 196 , 197 , 198 ]. For this review, we will limit our summary to strategies that aim to suppress myofibroblast actions but have not yet been considered or tested for implant fibrosis.…”

Section: Outlook: Lessons To Learn From Anti-fibrosis Strategies Against Cell Mechanosensing?mentioning

confidence: 99%

Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction

Noskovičová

Hinz

Pakshir

2021

Cells

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Body implants and implantable medical devices have dramatically improved and prolonged the life of countless patients. However, our body repair mechanisms have evolved to isolate, reject, or destroy any object that is recognized as foreign to the organism and inevitably mounts a foreign body reaction (FBR). Depending on its severity and chronicity, the FBR can impair implant performance or create severe clinical complications that will require surgical removal and/or replacement of the faulty device. The number of review articles discussing the FBR seems to be proportional to the number of different implant materials and clinical applications and one wonders, what else is there to tell? We will here take the position of a fibrosis researcher (which, coincidentally, we are) to elaborate similarities and differences between the FBR, normal wound healing, and chronic healing conditions that result in the development of peri-implant fibrosis. After giving credit to macrophages in the inflammatory phase of the FBR, we will mainly focus on the activation of fibroblastic cells into matrix-producing and highly contractile myofibroblasts. While fibrosis has been discussed to be a consequence of the disturbed and chronic inflammatory milieu in the FBR, direct activation of myofibroblasts at the implant surface is less commonly considered. Thus, we will provide a perspective how physical properties of the implant surface control myofibroblast actions and accumulation of stiff scar tissue. Because formation of scar tissue at the surface and around implant materials is a major reason for device failure and extraction surgeries, providing implant surfaces with myofibroblast-suppressing features is a first step to enhance implant acceptance and functional lifetime. Alternative therapeutic targets are elements of the myofibroblast mechanotransduction and contractile machinery and we will end with a brief overview on such targets that are considered for the treatment of other organ fibroses.

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Targeting the myofibroblast to improve wound healing

Cited by 6 publications

References 247 publications

The myofibroblast at a glance

The myofibroblast at a glance

The Role of Myofibroblasts in Physiological and Pathological Tissue Repair

Implant Fibrosis and the Underappreciated Role of Myofibroblasts in the Foreign Body Reaction

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