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In the research of experimental medicine, disease modeling is important for the development of treatment of diseases. There are two approaches to the disease modeling: a method using experimental animals and a method using cultured cells. In recent years, from the viewpoint of animal ethics, methods that do not use laboratory animals have become increasingly important. In this special issue, we welcome articles of original research and review regarding disease modeling without laboratory animals. This article collection is expected to contribute to the development of treatments for various human diseases while meeting the requirements of animal ethics by not using laboratory animals.