The myofibroblast at a glance

Abstract

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.

Evolving Roles of Muscle-Resident Fibro-Adipogenic Progenitors in Health, Regeneration, Neuromuscular Disorders, and Aging

“…Potentially, PDGFRα+ lineage-derived myofibroblasts are not the only players in stromal fibroproliferative-disorders and scarring. The participation of other tissue-resident perivascular cells (e.g., pericytes) or immune cells (e.g., MPs) to matrix remodeling upon injury, and the establishment of permanent scars, cannot be excluded (Henderson et al, 2013;Mederacke et al, 2013;Lemos and Duffield, 2018;Van Caam et al, 2018;Pakshir et al, 2020). For example, in tissues different from skeletal muscle (e.g., kidney), perivascular ADAM12+ progenitors that differentiate toward a myofibroblast-like phenotype when treated with TGF-β also contribute to tissue regeneration and fibrotic scarring following damage (Armulik et al, 2011;Lebleu et al, 2013;Birbrair et al, 2014).…”

“…Therefore, changes in matrix quantity and quality, increased matrix complexity and tissue stiffness may help tip the affected tissue into a self-perpetuating pathological state. In this abnormal setting, the bioavailability of damage-induced cues is magnified and may lead to scarring in response to insults that would generally be below the threshold required (Klingberg et al, 2014;Karsdal et al, 2017;Murray et al, 2017;Pakshir et al, 2020). Although significant progress in understanding these phenomena has been made at the tissue level, a big question in the muscle field has been identifying and characterizing the cell(s) that produce ectopic fibrous, fat, and bone in degenerated muscles.…”

Platelets, Constant and Cooperative Companions of Sessile and Disseminating Tumor Cells, Crucially Contribute to the Tumor Microenvironment

“…PDGF and TGFβ are strong stimulators for fibroblasts to differentiate into cancer-associated fibroblasts (CAFs) (Ostman, 2017;Lodyga and Hinz, 2020). CAFs convert the TME into a cancer cell-supportive environment by remodeling the ECM, by exerting mechanical forces and interstitial tension, and supporting tumor cell invasion (Kalluri, 2016;Eble and Niland, 2019;Pakshir et al, 2020). Another way of platelet-tumor cell-communications are microvesicles, which are secreted by platelets and are taken up by tumor cells in the TME (Goubran et al, 2015;Vajen et al, 2015).…”

Adult fibroblasts retain organ-specific transcriptomic identity

“…Fibroblasts, main players in fibrosis, have gained increased attention for their capacity to provide functions far beyond their canonical secretion of extracellular biological scaffolding and formation of scar tissue after injury. Recent literature poses the organ fibroblast as a major regulatory hub that senses local microenvironment imbalances and controls tissue remodeling [4] upon activation and phenotypic differentiation into the pro-fibrotic myofibroblast [5]. They are also involved in immunomodulation [6], by producing and responding to cytokines and activate immune cells of the innate and adaptive immune systems [7, 8], through organ-specific regulatory networks [9].…”