Review of the female Duroc/Yorkshire pig model of human fibroproliferative scarring

Abstract

Hypertrophic scarring after burns is an unsolved problem and remains as devastating today as it was in the 40s and it may be that the main reason for this is the lack of an accepted, useful animal model. The female, red Duroc pig was described as a model of hypertrophic scarring nearly 30 years ago but then vanished from the literature. This seemed strange since the authors reported that 12 of 12 pigs developed thick scar. In the mid 90s we explored the model and found that, indeed, the red Duroc pig does make thick scar. Other authors have established that the Yorkshire pig does not heal in this fashion so there is the possibility of a same species control. We have continued to explore the Duroc/ Yorkshire model and herein describe our experiences. Is it a perfect model of hypertrophic scarring? No. Is it a useful model of hypertrophic scarring? Time will tell. We have now obtained gene expression data from the Duroc/Yorkshire model and analysis is underway.Hypertrophic scarring is a significant negative outcome of a burn injury. Hypertrophic scars (HSs) are hard, raised, red, itchy, tender, and contracted. 1,2 These scars are ugly and uncomfortable and may diminish, but never completely go away. The resulting disfigurement and scarring affects quality of life, which, in turn, can lead to lowered self-esteem, social isolation, prejudicial societal reactions, and job discrimination. [3][4][5][6][7] Scarring may also have profound rehabilitation consequences including loss of physical function, impairment, disability, and difficulties pursuing recreational and vocational pursuits. 6,8,9 Literally hundreds of studies of collagen, fibroblasts, and growth factors in HSs have been performed over the past decades and yet the pathophysiology and treatment of this process are still essentially unknown. [10][11][12][13][14][15][16][17][18] It can be argued that the reason that the etiology of human HS is unknown is the absence of a useful animal model. [18][19][20][21][22] Mice, rats, rabbits, dogs, and cats have all failed to produce scar analogous to human HS. Repetitive literature searches have yielded few references to validated animal models of HS. Morris et al. 21 reported a scar model in the rabbit ear following a small full-thickness wound, but this is quite different from the human situation that involves large, partial-thickness wounds so the relationship is somewhat questionable. Since originally reported, this model has been adopted by one other group. 23 Xiang et al. 24 created 2×5 cm full-thickness wounds on rabbit ears but again the full-thickness model seems to differ from the human condition. Models that include human HS tissue implanted into athymic rats and mice have also been described. 22,[25][26][27][28][29][30][31] Since originally reported, these athymic models have been adopted by two other groups in two studies, 32,33 but this model seems very dissimilar to the clinical situations leading to HS formation in humans. Furthermore, the human transplanted tissue is established scar so any ear...

A Snapshot of Direct Cell–Cell Communications in Wound Healing and Scarring

“…However, things are looking up with recent reports of hypertrophic scar models in both pigs and mice. 11,12 Better understanding of the fibrotic process as the hypertrophic scar develops is a reasonable approach for identifying the techniques or procedures for the possible control of the excessive fibrosis associated with excessive scarring. The mast cell, the major inflammatory cell identified in developing hypertrophic scar, appears critical for promoting the fibrosis associated with hypertrophic scar.…”

Strategies Demonstrating Efficacy in Reducing Wound ContractionIn Vivo

“…Pig skin has similar physiological, anatomical, and biochemical properties to human skin. 12,13 With regard to studying epithelial and dermal repair, it is therefore the most appropriate model in the development of therapies for translation to clinical application (Fig. 1).…”

“…19 This mimics more closely the clinical situation of a large burn. However, the Yorkshire/Large White pig does not develop scar tissue akin to humans, 13 and longterm studies have not revealed significant effects on contraction. 19 Although the advantages and drawbacks of the animal models used in this field are apparent, a wealth of information on the physiological and biological response to therapies can be gained from using these models in experimental settings closely mimicking the clinical situation.…”

Mesenchymal Stem Cells: A Multimodality Option for Wound Healing

“…Porcine skin, in terms of dermal thickness, papillary structure, collagen composition, and distribution of dermal blood vessels, is the most comparable to humans among animal models currently used to study wound healing, including rodents, rabbits, and mini and large pigs. 11 Clinically, BM-MSCs have been shown to be safe and potentially efficacious in several phase I, II, and III clinical trials for a variety of diseases including myocardial infarction, chronic obstructive pulmonary disease, Crohn's disease, diabetes mellitus type 1, and stroke. 12 This wealth of clinical data on the safety of BM-derived MSCs warrants considering the use of these cells, as well as adipose-derived MSCs, in a wider range of applications, including wound repair.…”