Recent advances in the construction of humanized animal models and applications in translational medicine.

Over the past several decades, humanized mouse models have undergone significant refinement and become essential tools in biomedical research. Advances in genetic engineering, particularly the targeted knock-in of human cytokines, have enabled robust development and function of human immune cells in these models. Recent breakthroughs-including the directed differentiation of human pluripotent stem cells into thymic epithelial cells and the efficient expansion of hematopoietic stem cells-have alleviated the constraint of scarce human tissue sources. Furthermore, the reconstruction of lymph node structures and successful engraftment of solid organ tissues have significantly improved the efficiency and physiological relevance of human immune system reconstitution. These models now provide a unique platform for in vivo studies in cancer immunotherapy, infectious diseases, regenerative medicine, and autoimmune disorders under near-physiological conditions. Beyond rodents, substantial progress in humanized large animals, such as pigs, offers promising avenues for large-scale immune system reconstruction and mass production of immunotherapeutic cells. This review presents a comprehensive overview of the development, optimization, and expanding applications of humanized animal models, highlighting their transformative role in advancing translational medicine.