Scarless skin repair in immunodeficient mice

Abstract

Scarring, the end result of the wound healing process in adult mammals, is a problem of significant clinical importance. We observed that athymic nude-nu mice, similar to mammalian fetuses, are able to restore the structure and integrity of injured skin through a process resembling regeneration, where scar formation is absent. Among the postinjured skin tissues collected from athymic nude-nu, wild-type controls (C57BL/6J), severe-combined immunodeficient, Rag (lack of B and T cells), athymic (thymectomized neonates and adult C57BL/6J), and mice treated with an immunosuppressant (cyclosporin A), only athymic nude-nu mice showed: a lack of scar by histological examination (hematoxylin & eosin and Masson's trichrome staining), low levels of collagen (as determined by hydroxyproline content), high levels of hyaluronic acid, a statistically significant increase in elastic modulus for injured samples over unwounded (biomechanical testing) and low levels of the pro-scarring cytokines platelet-derived growth factor-B and transforming growth factor beta1. Additionally, immunohistochemical and Western blot analyses of postinjured tissues as well as flow cytometry analysis of blood samples showed the presence of CD8-positive cells in all studied animals except nude-nu mice. We conclude that scarless skin healing in athymic nude-nu mice provides a new model to study the influence of the immune system on tissue regeneration.

Assessment of Glycosuria and Bacterial Infections Amongst Prolonged – Healing Orthopaedic Wound Patients in Hospitals Within Imo State South Eastern Nigeria

“…Earlier studies [18,19] suggest that delayed T-cell infiltration along with decreased T-cell concentration in the wound site is associated with impaired wound healing, while others have reported that CD4+ cells (T-helper cells) have a positive role in wound healing and CD8+ cells (T-suppressor-cytotoxic cells) play an inhibitory role in wound healing. Interestingly, recent studies in mice deficient in both T-and B-cells have shown that scar formation is diminished in the absence of lymphocytes [20]. In the light of these findings, we conclude that microbial infections and glycosuria are major factors contributing to prolonged healing orthopaedic wounds in Imo State, south eastern Nigeria.…”

Effect of Citrus aurantium L. Essential Oil on Muscle Regeneration in Mdx Mice

“…Tissue repair cycles are monitored by a sequence of biochemical and cell events organized to restore the tissue integrity after the lesion. There is participation of the immune system acting in the protection of injured tissues against possible infections and in the secretion of growth factors such as cytokines, which metabolically change the morphological state of animal tissues (Park & Barbul, 2004;Gawronska-Kozak et al, 2006). Oral supplementation of NaCl decreases CK activity, but whether the inhibition of mdx muscle degeneration occurs before fiber necrosis remains unknown.…”

FOXN1 Transcription Factor in Epithelial Growth and Wound Healing

“…Interestingly, it was shown that epidermal Notch recruits a subset of inflammatory cells in the postwounding dermis in a non-cellautonomous way (49). It was assumed that that immunological defect does not have a direct impact on the mechanism of wound healing in nude mice (50). However, earlier studies showed that T-cell deficiency in the skin of nude mice leads to enhanced breaking strength and collagen deposition, which were reduced to the values observed in wild-type controls when syngeneic T lymphocytes were reconstructed (51).…”

“…The skin of Foxn1-deficient mice is thicker and hyperplastic (16), exhibits distinctive biochemical and physical characteristics (50), and in general, seems to display immature embryonic features (17). It was reported that the spatiotemporal expression pattern of specific keratins in the IFE of nude mice is altered.…”

“…It was shown that Foxn1-deficient mice are an example of a regeneration model in mammals (15,50,54). Ear holes made with a 4-mm punch were regrown with signs of regeneration reminiscent of rapid reepithelialization, blastemalike structure formation, and chondrogenesis (54).…”