Abstract 2790: Establishment and characterization of human skingraft model in immunodeficient mice.

Abstract

Abstract The humanization process of mice with various tissues named Chi-mice aimed to reproduce better the human situation and to be more predictive than conventional models. In order to evaluate new targeting therapies or adverse side effects involving skin components, pre-clinical studies need to be assayed with new molecules in adequate and validated mouse models bearing human skin. The collection of skin samples was done under ethically approved master agreements and with the signed consent of each patient. The patient's clinical history, the serology results (HIV, HBV and HCV) and tissue banking were centralized in our internal approved biological resource center. To develop such models, we used skins of different origins including foreskin, breast and abdomen that were isolated by different methods (full recovery of about 1 cm depth sample or dermatomization of the 1-2 mm epidermal/dermal layer). These samples were xenografted on immune deficient NOD-SCID mice under different conditions including matrigel grafting. After one month implantation, skingrafts were collected and observed microscopically to confirm the preservation of human organization of skin by full histology. Also, the species nature of vessels was characterized by immunochemistry to evaluate the host penetration within human skingraft and both CD-31 positive mouse and human vessels were found in the skingraft. In the context of vascular leak syndrome (VLS) induction by IL2 treatment, we have used the wet/dry ratio of skingraft to measure the induced-edema and we have measured the blue evans uptake in those injured skingraft to appreciate the epidermal vasculature leaking. Anapathological comparisons were also performed to reveal the histological modifications observed during VLS. These different characterizations performed during development of the skingraft model enabled us to obtain human skin xenografted on mice that retained the human characteristics of the primary material. The co-implantation of other human tissue (tumor) with skin in same mice which refined better the humanized model will be presented. The use of fresh skin and various tissues in drug discovery and early preclinical development of new therapies aimed at corroborating results with clinical reality. Altogether, these processes from the clinical sample collection to the in vivo drug efficacy study through ex vivo assays should help the preclinical drug selection, development and clinical positioning as well as companion biomarker identification. Citation Format: Guillaume Serin, Loïc Morgand, Marie Leblanc, Francis Bichat. Establishment and characterization of human skingraft model in immunodeficient mice. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2790. doi:10.1158/1538-7445.AM2013-2790