Animal Disease Models and Patient-iPS-Cell-Derived In Vitro Disease Models for Cardiovascular Biology—How Close to Disease?

SIMPLE SUMMARY: Currently, rodents and pigs are the primary disease models used in cardiovascular research. Generally, larger animals that are more closely related to humans are better-suited disease models. However, they can have restricted or limited use because they are difficult to handle and maintain. Animal welfare laws regulate experimental animals. Different species have different mechanisms of disease onset. Organs in each animal species have different characteristics depending on their evolutionary history and living environment. For example, mice have higher heart rates than humans. Nonetheless, preclinical studies have used animals to evaluate the safety and efficacy of human drugs because no other complementary method exists. We need to evaluate the similarities and differences in disease mechanisms between humans and experimental animals, and the translation of animal data to humans can be helpful in this evaluation. In vitro disease models can also be used as human disease models. Three-dimensional human cardiomyocyte cultures are generated from patient-derived induced pluripotent stem cells (iPSCs), which are genetically identical to the derived patient. In this review, we explore the possible use of animal disease models, iPSC-derived in vitro disease models, humanized animals, and the recent challenges of machine learning in making the models more similar to human diseases. ABSTRACT: Currently, zebrafish, rodents, canines, and pigs are the primary disease models used in cardiovascular research. In general, larger animals have more physiological similarities to humans, making better disease models. However, they can have restricted or limited use because they are difficult to handle and maintain. Moreover, animal welfare laws regulate the use of experimental animals. Different species have different mechanisms of disease onset. Organs in each animal species have different characteristics depending on their evolutionary history and living environment. For example, mice have higher heart rates than humans. Nonetheless, preclinical studies have used animals to evaluate the safety and efficacy of human drugs because no other complementary method exists. Hence, we need to evaluate the similarities and differences in disease mechanisms between humans and experimental animals. The translation of animal data to humans contributes to eliminating the gap between these two. In vitro disease models have been used as another alternative for human disease models since the discovery of induced pluripotent stem cells (iPSCs). Human cardiomyocytes have been generated from patient-derived iPSCs, which are genetically identical to the derived patients. Researchers have attempted to develop in vivo mimicking 3D culture systems. In this review, we explore the possible uses of animal disease models, iPSC-derived in vitro disease models, humanized animals, and the recent challenges of machine learning. The combination of these methods will make disease models more similar to human disease.