Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells
Yash Agarwal, Cole Beatty, Sara Ho, Lance R. Thurlow, Antu Das, Samantha Kelly, Isabella Castronova, Rajeev Salunke, Shivkumar Biradar, Tseten Yeshi, Anthony R. Richardson, Moses T. Bility
Abstract
Abstract The human skin is a significant barrier for protection against pathogen transmission. Rodent models used to investigate human-specific pathogens that target the skin are generated by introducing human skin grafts to immunocompromised rodent strains. Infection-induced immunopathogenesis has been separately studied in humanized rodent models developed with human lymphoid tissue and hematopoietic stem cell transplants. Successful co-engraftment of human skin, autologous lymphoid tissues, and autologous immune cells in a rodent model has not yet been achieved, though it could provide a means of studying the human immune response to infection in the human skin. Here, we introduce the human Skin and Immune System (hSIS)-humanized NOD- scid IL2Rγ null (NSG) mouse and Sprague–Dawley-Rag2 tm2hera Il2rγ tm1hera (SRG) rat models, co-engrafted with human full-thickness fetal skin, autologous fetal lymphoid tissues, and autologous fetal liver-derived hematopoietic stem cells. hSIS-humanized rodents demonstrate the development of human full-thickness skin, along with autologous lymphoid tissues, and autologous immune cells. These models also support human skin infection following intradermal inoculation with community-associated methicillin-resistant Staphylococcus aureus . The co-engraftment of these human skin and immune system components into a single humanized rodent model could provide a platform for studying human skin infections.