Characterization of Hypertrophic Scar Formation in Nude and Knockout Mice Deficient in T, B and Natural Killer Cells.

摘要

Introduction: Hypertrophic scar (HSc) is a fibroproliferative disorder lacking a relevant animal model. Our objective is to characterize proliferative scars in human xenografts generated after grafting human skin onto mice deficient in T, B and natural killer cells.;Results: Xenografting nude mice with human skin results in scars morphologically, histologically and immunohistochemically similar to human HSc. Knockout animals developed similar scars and demonstrate greater capacity for scar remodeling.;Conclusion: Proliferative xenograft scars in knockout animals better represent the natural history of HSc. The role of activated, profibrotic fibrocytes and macrophages in these animals requires further investigation.;Methods: Nude, T-cell receptor (TCR) beta-/-delta -/-, RAG(recombination activating gene)-1-/- and RAG-2 -/-gammac-/- mice were xenografted with split thickness human skin. Controls were autografted with mouse skin. Animals were euthanized at 30, 60, 120 and 180 days postoperatively. Scar biopsies were subjected to hematoxylin and eosin, Masson's trichrome, toluidine blue and picrosirius red staining. Immunohistochemistry included anti-human HLA-ABC, alpha--smooth muscle actin, decorin and biglycan staining.