The Importance of Mast Cells in Dermal Scarring

Wilgus, Traci A.; Wulff, Brian C.

doi:10.1089/wound.2013.0457

Cited by 88 publications

(61 citation statements)

References 82 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Under pathological conditions, an increase of mast cell number is often associated with elastinrelated tissue fibrosis. [35,36] In a skin photodamage model, chronic ultraviolet light exposure increases skin mast cell number accompanied by a 3.6 fold elevation in elastin content, which was not observed in the mast cell-deficient Kit W/W-v mice. [37] Similar correlation was also present in human skin.…”

Section: Discussionmentioning

confidence: 99%

Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice

Lawrence

Wadsworth

et al. 2017

View full text Add to dashboard Cite

How to cite this article: Wu J, Lawrence C, Wadsworth RM, Kennedy S. Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice. Vessel Plus 2017;1:137-44.Aim: Mast cells are versatile innate immune cells and are reported to promote vascular inflammation and neointimal lesion formation, thereby contributing to the development of vascular stenosis and atherosclerosis. However, it is not clear whether mast cells also regulate vascular matrix remodelling in established neointima. This study addressed the hypothesis that perivascular mast cells regulate neointimal matrix remodelling using a mouse vein graft model. Methods: The impact of mast cells on neointimal remodelling was investigated using mast cell-deficient animals in both normolipidaemic (Kit W-sh/W-sh ) and hyperlipidaemic (apoEconditions. The effect of perivascular mast cells on vascular matrix remodelling, including collagen and elastin deposition, was investigated using a local mast cell reconstitution method that selectively repopulated mast cells around the carotid artery (where the vein graft was inserted) in Kit W-sh/W-sh mice. Results: In normolipidaemic vein grafts (Kit W-sh/W-sh vs. the wild type control C57BL/6J), collagen synthesis was not affected by mast cell deficiency at 4 weeks. In contrast, neointimal elastin was reduced by 6.5-fold in mast cell-deficient Kit W-sh/W-sh mice, which was prevented by perivascular mast cell reconstitution. Mast cell deficiency induced a similar reduction in neointimal elastin in hyperlipidaemic mice (apoE -/-Kit W-sh/W-sh vs. apoE -/-), with a significant increase in cell proliferation and neointimal area at 4 weeks. Conclusion: Mast cells appear to promote elastin deposition in vein grafts and this may lead to further suppression of cell proliferation and neointimal thickening under hyperlipidaemic conditions. Key words:Mast cells, elastin, chronic restenosis, neointima, vein graft ABSTRACTArticle history:

show abstract

Section: Discussionmentioning

confidence: 99%

Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice

Lawrence

Wadsworth

et al. 2017

View full text Add to dashboard Cite

show abstract

“…23 They promote inflammation, reepithelialization, and increased vascular permeability and angiogenesis. 38 Moreover, histamine increases fibroblast proliferation and its differentiation into the contractile myofibroblast. 39 Several studies have shown mast cell involvement in scar formation by affecting collagen maturation and remodeling 40,41 Although increased mast cell num-ber and activity occurs in HTS, 42 lower mast cell numbers have been found in scarless regenerative wound healings such as fetal wounds and oral mucosal wounds.…”

Section: Discussionmentioning

confidence: 99%

A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full Thickness Human Skin Grafts

Alrobaiea

Ding

et al. 2016

Advances in Wound Care

View full text Add to dashboard Cite

Objective: Hypertrophic scar (HTS) is a dermal form of fibroproliferative disorder that develops following deep skin injury. HTS can cause deformities, functional disabilities, and aesthetic disfigurements. The pathophysiology of HTS is not understood due to, in part, the lack of an ideal animal model. We hypothesize that human skin with deep dermal wounds grafted onto athymic nude mice will develop a scar similar to HTS. Our aim is to develop a representative animal model of human HTS. Approach: Thirty-six nude mice were grafted with full thickness human skin with deep dermal scratch wound before or 2 weeks after grafting or without scratch. The scratch on the human skin grafts was made using a specially designed jig that creates a wound >0.6 mm in depth. The xenografts were morphologically analyzed by digital photography. Mice were euthanized at 1, 2, and 3 months postoperatively for histology and immunohistochemistry analysis. Results: The mice developed raised and firm scars in the scratched xenografts with more contraction, increased infiltration of macrophage, and myofibroblasts compared to the xenografts without deep dermal scratch wound. Scar thickness and collagen bundle orientation and morphology resembled HTS. The fibrotic scars in the wounded human skin were morphologically and histologically similar to HTS, and human skin epithelial cells persisted in the remodeling tissues for 1 year postengraftment. Innovation and Conclusions: Deep dermal injury in human skin retains its profibrotic nature after transplantation, affording a novel model for the assessment of therapies for the treatment of human fibroproliferative disorders of the skin. INTRODUCTIONSkin wound healing is an extremely complex process that involves the reactions and interactions of inflammatory cells, growth factors, and cytokines.1 This orchestrated process can be divided into four overlapped phases starting with hemostasis, followed by inflammation and proliferation, and ending by maturation, including collagen remodeling to restore the damaged skin integrity through formation of a mature scar.

show abstract

“…The skin mast cells play a fundamental role in the regulation of inflammation due to secretion of chemical mediators such as histamine, glycosaminoglycans and cytokines that act directly on the resolution of inflammation by promoting cell proliferation, differentiation, migration and tissue remodeling [Ng, 2010]. Although mast cells have been associated with fibrogenesis and are necessary for normal wound healing [Weller et al, 2006;Wilgus and Wulff, 2014], the role of these cells in skin repair is still uncertain, with a recent study indicating that they are not required for the healing of cutaneous excisional wounds in mice [Nauta et al, 2013]; this warrants further investigation. The synthesis of components of the extracellular matrix, particularly collagen, is an important factor that determines the quality of the tissue repair process [Webb and Dyson, 2003;Steinstraesser et al, 2010].…”

Section: Discussionmentioning

confidence: 99%

<b><i>Bathysa cuspidata</i></b> Extract Modulates the Morphological Reorganization of the Scar Tissue and Accelerates Skin Wound Healing in Rats: A Time-Dependent Study

Gonçalves

Novaes²,

Cupertino³

et al. 2014

Cells Tissues Organs

View full text Add to dashboard Cite

The technological development of pharmaceutical products based on plant extracts is currently responsible for a large number of recent innovations in healthcare. The objective of this study was to develop and investigate the effect and potential applicability of an ointment-based Bathysa cuspidata extract (BCE) for the management of skin wounds in rats. Threeskin wounds of 12 mm in diameter were made on the backs of the animals, which were randomized into 4 groups according to the application received, i.e. the SAL group: 0.9% saline solution, the LAN group: lanolin, the BCE 2.5% group: 2.5% BCE emulsified in lanolin and the BCE 5% group: 5% BCE emulsified in lanolin. The applications were made daily over 21 days, and every 7 days tissue from different wounds was removed. On days 7, 14 and 21, the BCE 2.5% and BCE 5% groups showed the best results in relation to wound closure, and a higher proportion (in length, density and volume) of blood vessels and fibroblasts compared to the other groups. On days 7 and 14, there was a significant increase in the number of mast cells in these 2 groups when compared to the SAL and LAN groups. On day 21, they also had a higher proportion of collagen I than collagen III. B. cuspidata in an ointment base was effective in stimulating tissue cellularity, mast cell recruitment, neoangiogenesis, synthesis and maturation of collagen, epidermal thickness and surface area in scar tissue. These events were potentially related to the best quality and speed for skin regeneration in the rats treated with the BCE ointment.

show abstract

The Importance of Mast Cells in Dermal Scarring

Cited by 88 publications

References 82 publications

Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice

Perivascular mast cells promote neointimal elastin deposition and suppress chronic vein graft restenosis in hyperlipidaemic mice

A Novel Nude Mouse Model of Hypertrophic Scarring Using Scratched Full Thickness Human Skin Grafts

<b><i>Bathysa cuspidata</i></b> Extract Modulates the Morphological Reorganization of the Scar Tissue and Accelerates Skin Wound Healing in Rats: A Time-Dependent Study

Contact Info

Product

Resources

About