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To translate research findings into medicine and drug development, we have been performing in vivo research using primary human samples. Development of mouse models with reconstituted human immunity would be critical to overcome technical and ethical constraints associated with in vivo human research. To this end, we have created humanized mice by intravenously injecting purified human hematopoietic stem cells (HSCs) into immune-compromised NOD/SCID/IL2rgKO newborns. This xenogeneic transplantation system allows long-term engraftment and multi-lineage differentiation of human HSCs. The humanized mouse fully reconstituted with human myeloid and lymphoid subsets is expected to serve as an in vivo platform for the investigation of human immune function. In addition to understanding normal human hematopoiesis and immunity, the use of humanized mice is expected to allow investigators to translate their research findings into therapeutic and pharmaceutical development. As a possibility for such translation, we developed an in vivo model of human acute myeloid leukemia (AML), a disease in which the majority of patients succumb to relapse. Using the model, we examined the pathogenesis of AML and tried to clarify the role of AML stem cells in chemotherapy resistance and relapse. Humanized mouse model for both normal and diseased immuno-hematopoietic system is opening a new era in translational medicine.

"Creation of mouse models for human diseases"