Characterization of the skin keloid microenvironment

Abstract

Keloids are a fibroproliferative skin disorder that develops in people of all ages. Keloids exhibit some cancer-like behaviors, with similar genetic and epigenetic modifications in the keloid microenvironment. The keloid microenvironment is composed of keratinocytes, fibroblasts, myofibroblasts, vascular endothelial cells, immune cells, stem cells and collagen fibers. Recent advances in the study of keloids have led to novel insights into cellular communication among components of the keloid microenvironment as well as potential therapeutic targets for treating keloids. In this review, we summarized the nature of genetic and epigenetic regulation in keloid-derived fibroblasts, epithelial-to-mesenchymal transition of keratinocytes, immune cell infiltration into keloids, the differentiation of keloid-derived stem cells, endothelial-to-mesenchymal transition of vascular endothelial cells, extracellular matrix synthesis and remodeling, and uncontrolled angiogenesis in keloids with the aim of identifying new targets for therapeutic benefit.

Dual-wavelength dye laser combined with betamethasone injection for treatment of keloids: protocol of a randomised controlled trial

“…Keloids, characterised by raised and disfigured tissue resulting from aberrant wound healing, pose a therapeutic challenge due to the multifactorial nature of scar formation. 27 Current treatments primarily aim to suppress fibroblast proliferation, curb collagen deposition and alleviate inflammation in addressing keloids. However, these therapies exhibit a propensity for relapse and seldom achieve complete resolution.…”

Artificial keloid skin models: understanding the pathophysiological mechanisms and application in therapeutic studies

“…To create an artificial keloid skin that faithfully mimics the actual keloid skin structure, inflammatory mechanisms as well as microenvironment, composed of various types of cells such as fibroblast, myofibroblast, keloid-derived stem cells, macrophages, mast cells and neutrophils, 120 with multiple activated signaling pathways, such as TGF-β/Smad, YAP/TAZ, α1β1 or αvβ3, it is particularly crucial to reproduce cell proliferation, differentiation, migration, collagen synthesis, expression of profibrotic genes, keloid-relative receptor expression and cell–cell communication. 121–125 In controlling these aspects, matrix scaffolds play a significant role in contributing to cell attachment, support, and behaviour.…”

Insights into the role of adipose-derived stem cells and secretome: potential biology and clinical applications in hypertrophic scarring

“…The pathogenesis of HTS has not yet been clarified, and it is generally accepted that it may be related to the persistent inflammatory response and abnormal proliferation of fibroblasts, excessive vascular regeneration, and excessive extracellular matrix (ECM) deposition [ 3 , 8 ]. HTS usually occurs in areas where the skin has been stretched, protrudes from the wound site, and grows rapidly over a period of 4–12 weeks, and once formed is difficult to recover as before [ 9 , 10 ]. Clinical treatment of pathologic scarring is complex and difficult, and currently available treatments include localized compression, laser therapy, steroid injections, and surgical excision [ 11 ].…”

“…When skin trauma occurs, ADSCs and mature adipocytes mediate the inflammatory response and regulate the proliferation and activation of fibroblasts through paracrine secretion of a variety of cytokines, which has a certain therapeutic effect on dermal fibrosis and refractory scarring [ 15 – 17 ]. In addition, progressive reduction of intradermal adipocytes is a common pathology in many dermatofibrotic diseases [ 9 , 18 ]. Last but not least, most patients would welcome the removal of some excess fat [ 19 ].…”

“…Fibroblast activation and function are important for wound healing, but in pathological scarring, activation of fibroblasts themselves may lead to fibroblast deposition and scar formation [ 9 , 111 ]. In pathological scarring, increased fibroblasts secrete TGF-β1, which reduces the dependence of fibroblasts on external growth stimulators and maintains a strong proliferative ability [ 112 ].…”