Managing keloid scars: From radiation therapy to actual and potential drug deliveries

Huang, Chenyu; Liu, Longwei; You, Zhifeng; Du, Yanan; Ogawa, Rei

doi:10.1111/iwj.13104

Cited by 46 publications

(48 citation statements)

References 80 publications

(130 reference statements)

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“…36,37 Indeed, injections with IFN-α and -γ have been used in the clinic to reduce the size of keloids, although the results are conflicting. 38 The study in African American keloid patients that was described above found that the PBMCs from these patients secreted more IFN-β but less IFN-α and -γ than control subjects. 24…”

Section: Other Cytokines That Play Key Roles In Keloid Pathogenesismentioning

confidence: 90%

Systemic factors that shape cutaneous pathological scarring

Huang

Ogawa

2020

FASEB j.

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Cutaneous pathological scars are fibrotic lesions that grow continuously, invade the adjacent skin, and are erythematous, itchy, and painful. Their etiology remains unclear but may involve genetic, local mechanical, and systemic factors. Here, we will summarize the main systemic factors that shape cutaneous pathological scarring, especially keloid formation and aggravation. They include circulating cytokines, chemokines, growth factors, particular cell types, sex hormones, the systemic renin‐angiotensin system, and vitamin D, all of which directly shape the angiogenesis, inflammation, fibrosis, and remodeling in pathological scars. There are also several environmental factors that more indirectly influence pathological scar formation or progression, namely diet, smoking, psychological stress, and exercise. Notably, much of the evidence on these systemic factors focus on their effects on one pathological scar characteristic, namely their fibrosis. However, systemic factors probably also shape other pathological scar characteristics. We describe two new avenues of keloid research that may greatly improve our understanding of pathological scarring and the systemic factors that affect it. One is the multiple similarities between keloids and tumors; the other is the different stem‐cell populations in keloids. We expect this research will greatly aid the development of diagnostic biomarkers for cutaneous pathological scars and drugs/techniques/regimens that prevent, improve, or cure these scars.

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Section: Other Cytokines That Play Key Roles In Keloid Pathogenesismentioning

confidence: 90%

Systemic factors that shape cutaneous pathological scarring

Huang

Ogawa

2020

FASEB j.

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“…First, pathological scars are characterized by chronic inflammation: this inflammation is particularly evident at the invasive edges of keloids and causes the erythematous and pruritic symptoms of these scars. This inflammation plays a key role in the development and progression of pathological scars, as demonstrated by the widely recognized beneficial effects of intralesional administration of anti-inflammatory drugs such as corticosteroid [3]. It is likely that this inflammation promotes excessive local angiogenesis, endothelial dysfunction, and vascular hyperpermeability that in turn facilitates the continued influx of inflammatory cells and factors, thereby setting up a vicious cycle of inflammation and abnormal vascular activities [4].…”

Section: Introductionmentioning

confidence: 99%

The Vascular Involvement in Soft Tissue Fibrosis—Lessons Learned from Pathological Scarring

Huang

Ogawa

2020

IJMS

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Soft tissue fibrosis in important organs such as the heart, liver, lung, and kidney is a serious pathological process that is characterized by excessive connective tissue deposition. It is the result of chronic but progressive accumulation of fibroblasts and their production of extracellular matrix components such as collagens. Research on pathological scars, namely, hypertrophic scars and keloids, may provide important clues about the mechanisms that drive soft tissue fibrosis, in particular the vascular involvement. This is because these dermal fibrotic lesions bear all of the fibrotic characteristics seen in soft tissue fibrosis. Moreover, their location on the skin surface means they are readily observable and directly treatable and therefore more accessible to research. We will focus here on the roles that blood vessel-associated cells play in cutaneous scar pathology and assess from the literature whether these cells also contribute to other soft tissue fibroses. These cells include endothelial cells, which not only exhibit aberrant functions but also differentiate into mesenchymal cells in pathological scars. They also include pericytes, hepatic stellate cells, fibrocytes, and myofibroblasts. This article will review with broad strokes the roles that these cells play in the pathophysiology of different soft tissue fibroses. We hope that this brief but wide-ranging overview of the vascular involvement in fibrosis pathophysiology will aid research into the mechanisms underlying fibrosis and that this will eventually lead to the development of interventions that can prevent, reduce, or even reverse fibrosis formation and/or progression.

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“…The ethiopathogenesis of keloid formation has still remained poorly understood even though etiology is becoming clearer to date . It has been suggested that keloid scarring is caused by an inability to stop the normal wound healing process .…”

Section: Introductionmentioning

confidence: 99%

“…There are no keloid specific treatment that can make the keloid to completely disappear from the affected anatomical area. All current treatment modalities are associated with high recurrence rates . The approaches to keloid treatment involve either ablative surgery with radiation or injection of different pharmacological substances into the keloid mass.…”

Section: Introductionmentioning

confidence: 99%

“…The approaches to keloid treatment involve either ablative surgery with radiation or injection of different pharmacological substances into the keloid mass. The aim of every modality is to make keloid mass smaller and less symptomatic . Triamcinolone acetate (TAC) has been the mostly used substance by far, with proven efficacy in many patients .…”

Section: Introductionmentioning

confidence: 99%

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Histopathology and immunohistochemical analysis of 5‐fluorouracil and triamcinolone treated keloids in double‐blinded randomized controlled trial

Hietanen

Järvinen

Tolonen

et al. 2020

Wound Repair Regeneration

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Keloids are a major complication related to surgical wound healing and very challenging condition to treat. Many treatment options are available, but the efficacy of the treatment is poor in most of cases and some keloids do not respond to the treatment at all. We compared the efficacy of intralesional 5-fluorouracil (5-FU) and triamcinolone (TAC) injections in a double-blind randomized controlled trial (RCT). Forty-three patients with 50 keloid scars were treated with either intralesional TAC or 5-FUinjections over 6 months. We wanted to find out whether biological features (cell density, cell proliferation rate, vascular density, myofibroblast numbers, steroid hormone receptor expression) in keloids could be used to predict the response to therapy and define the biological changes that take place in patients receiving a response. As there was no statistically significant difference in the remission rate between TAC and 5-FU treatments, all patients were combined and analyzed as responders and nonresponders. Although responders have slightly more myofibroblasts than the nonresponders in their keloids in the pretreatment biopsy samples, we could not identify a single predictive factor that could identify those patients that respond to drug injections. The good clinical response to therapy is associated with the simultaneous reduction of myofibroblasts in the keloid. This study demonstrates that myofibroblasts are reduced in number in those keloids that were responsive to therapy, and that both 5-FU and TAC injections are useful for keloid treatment.

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Managing keloid scars: From radiation therapy to actual and potential drug deliveries

Cited by 46 publications

References 80 publications

Systemic factors that shape cutaneous pathological scarring

Systemic factors that shape cutaneous pathological scarring

The Vascular Involvement in Soft Tissue Fibrosis—Lessons Learned from Pathological Scarring

Histopathology and immunohistochemical analysis of 5‐fluorouracil and triamcinolone treated keloids in double‐blinded randomized controlled trial

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