Abstract:Keloids are locally exuberant dermal scars characterized by excessive fibroblast proliferation and matrix accumulation. Although treatment strategies include surgical removal and intralesional steroid injections, an effective regimen is yet to be established due to a high rate of recurrence. The regressing center and growing margin of the keloid have different collagen architecture and also differ in the rate of proliferation. To investigate whether proliferation is responsive to collagen topography, keloid, s… Show more
“…Simple organotypic keloid models involve the culturing of keloid derived fibroblasts in bovine/rat type I collagen matrices, without any epidermal keratinocytes. Such collagen‐derived dermal scaffolds can range from simple layer of collagen to nano‐patterned collagen matrices populated with dermal fibroblasts . A vast body of research community has dedicated their time into development of such organotypic skin models over the past years, therefore we will explore just a few of those studies.…”
Keloid scars are described as benign fibro‐proliferative dermal outgrowths that commonly occur in pigmented skin post cutaneous injury, and continue to grow beyond the boundary of the original wound margin. There is a lack of thorough understanding of keloid pathogenesis and thus keloid therapeutic options remain ill‐defined. In view of the poor response to current therapy and high recurrence rates, there is an unmet need in improving our knowledge and therefore in identifying targeted and effective treatment strategies in management of keloids. Keloid research however, is hampered by a lack of relevant animal models as keloids do not spontaneously occur in animals and are unique to human skin. Therefore, developing novel animal models and nonanimal models for functional evaluation of keloid cells and tissue for better understanding their pathobiology and response to putative candidate therapies are essential. Here, we present the key concepts and relevant emerging research on two‐dimensional and three‐dimensional cell and tissue models for functional testing of keloid scars. We will describe in detail current models including in vitro mono‐ and co‐cultures, multi‐cellular spheroids (organoids) and organotyopic cultures, ex vivo whole skin keloid tissue organ culture models as well as in vivo human patient models. Finally, we discuss the role played by time as the fourth dimension in a novel model that involves sequential temporal biopsies of human patients with keloids (a so called 4D in vivo human model). The use of these unique models will no doubt prove pivotal in identification of new drug targets as well as biomarkers, in functional testing of emerging novel therapeutics, and in enhancing our understanding of keloid disease biology.
“…Simple organotypic keloid models involve the culturing of keloid derived fibroblasts in bovine/rat type I collagen matrices, without any epidermal keratinocytes. Such collagen‐derived dermal scaffolds can range from simple layer of collagen to nano‐patterned collagen matrices populated with dermal fibroblasts . A vast body of research community has dedicated their time into development of such organotypic skin models over the past years, therefore we will explore just a few of those studies.…”
Keloid scars are described as benign fibro‐proliferative dermal outgrowths that commonly occur in pigmented skin post cutaneous injury, and continue to grow beyond the boundary of the original wound margin. There is a lack of thorough understanding of keloid pathogenesis and thus keloid therapeutic options remain ill‐defined. In view of the poor response to current therapy and high recurrence rates, there is an unmet need in improving our knowledge and therefore in identifying targeted and effective treatment strategies in management of keloids. Keloid research however, is hampered by a lack of relevant animal models as keloids do not spontaneously occur in animals and are unique to human skin. Therefore, developing novel animal models and nonanimal models for functional evaluation of keloid cells and tissue for better understanding their pathobiology and response to putative candidate therapies are essential. Here, we present the key concepts and relevant emerging research on two‐dimensional and three‐dimensional cell and tissue models for functional testing of keloid scars. We will describe in detail current models including in vitro mono‐ and co‐cultures, multi‐cellular spheroids (organoids) and organotyopic cultures, ex vivo whole skin keloid tissue organ culture models as well as in vivo human patient models. Finally, we discuss the role played by time as the fourth dimension in a novel model that involves sequential temporal biopsies of human patients with keloids (a so called 4D in vivo human model). The use of these unique models will no doubt prove pivotal in identification of new drug targets as well as biomarkers, in functional testing of emerging novel therapeutics, and in enhancing our understanding of keloid disease biology.
“…In addition, these cells have higher rates of mitosis, and lower rates of apoptosis. [6,9,10,11] There are several theories of keloid formation according to induced factor. Some of them implicate certain cytokines, other implicate keratinocyte.…”
Section: Remodelling or Maturation Phasementioning
confidence: 99%
“…Keloid lesions were found to have lower rates of apoptosis than normal skin, because downregulation of apoptosis-related genes, including p53 [6,9,11,17].…”
Section: The Following Are the Most Important Theoriesmentioning
“…The pathogenesis of keloids has been related to the alterations in cell proliferation and migration, synthesis and secretion of extracellular matrix proteins, and inflammatory responses (Machesney et al, 1998;Tredget et al, 1997;Muthusubramaniam et al, 2014). Cytokines and chemokines have been involved in various tissue-specific inflammatory events, cancer metastasis, and fibrosis.…”
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