An Infection Model for SARS-CoV-2 Using Rat Transplanted with hiPSC-Airway Epithelial Cells

Abstract

Investigating the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the airway epithelium and developing effective defense strategies against infection are important. To achieve this, establishing appropriate infection models is crucial. Therefore, various in vitro models, such as cell lines and primary cultures, and in vivo models involving animals that exhibit SARS-CoV-2 infection and genetically humanized animals have been used as animal models. However, no animal model has been established that allows infection experiments with human cells under the physiological environment of airway epithelia. Therefore, we aimed to establish a novel animal model that enables infection experiments using human cells. Human induced pluripotent stem cell-derived airway epithelial cell-transplanted nude rats (hiPSC-AEC rats) were used, and infection studies were performed by spraying lentiviral pseudoviruses containing SARS-CoV-2 spike protein and the GFP gene on the tracheae. After infection, immunohistochemical analyses revealed the existence of GFP-positive-infected transplanted cells in the epithelial and submucosal layers. In this study, a SARS-CoV-2 infection animal model including human cells was established mimicking infection through respiration, and we demonstrated that the hiPSC-AEC rat could be used as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.

Impact Statement

Infection models are important to elucidate the mechanism of infection and to develop defense or therapeutic methods against infection; however, no research model permitting infection experiments with human cells under the physiological environment of airway epithelial tissue has been established. Therefore, we aimed to establish a novel infection model mimicking infection through respiration using human cells, performed infection experiments by spraying pseudovirus into hiPSC-AEC rats, and confirmed infection in human cells. This infection model could serve as an animal model for basic research and the development of therapeutic methods for human-specific respiratory infectious diseases.