Keloids: Animal models and pathologic equivalents to study tissue fibrosis

Abstract

Animal models are crucial for the study of fibrosis. Keloids represent a unique type of fibrotic scarring that occurs only in humans, thus presenting a challenge for those studying the pathogenesis of this disease and its therapeutic options. Here, several animal models of fibrosis currently in use are described, emphasizing recent progress and highlighting encouraging challenges.

Keywords: Animal models; Hypertrophic scar; Keloids; Tissue fibrosis.

Figure 1. Tsk/+ and Bleomycin Models

Hematoxylin & Eosin and Masson’s Trichrome staining of wild-type +/+ (A, C), Tsk/+ (B, D), PBS-treated (E,F) and bleomycin-treated (G, H) cutaneous sections. Genetic mutation in fibrillin-1 gene in the Tsk/+ mouse leads to thickened dermis with abundant collagen in both upper and lower dermis (B & D, sub-panniculus carnosus) compared to control (A & C). Daily administration of bleomycin elicits a strong inflammatory reaction in the host animal which, in turn, leads to increased dermal thickness and fibrosis (A & C) compared to control (B & D). Images of Tsk mouse reproduced from: Manne, J., Markova, M., Siracusa, L., Jimenez, S.A. “Collagen content in skin and internal organs of the Tight Skin Mouse: An animal model of scleroderma. Biochemistry Research International. Vol 2013, 1–8.

Figure 2. Bio-Scaffold Model

PLA scaffolds (B & C) are dynamically seeded and subcutaneously implanted into immune-deficient mice (A). Upon retrieval, the scaffolds demonstrate marked neovascularization from the host animal, and continued collagen production (D, E: H&E staining, F: Sirius red staining).