[Xenotransplantation assay for cancer stem cells]

Immunodeficient mice are widely used to reconstitute human hematopoiesis by xenotransplantation of hematopoietic stem cells(HSCs). This humanized mouse model provides a powerful tool to evaluate biological properties of human HSCs in vivo. This systems have been used also to study human cancer stem cells. Currently, NOD -background immunodeficient strains are the most efficient to reconstitute human hematopoiesis in the mice, but even they are not enough for cancer stem cell assay. NOD strain has multiple immune deficiencies. For this reason, to improve and establish a new xenotransplantation model, lymphoid-depleted strains have been backcrossed into the NOD-inbred strain to introduce such numerous NOD-specific abnormalities. Our positional genetic study has located the NOD-specific polymorphic Sirpa as a molecular responsible for its high xenograft efficiency. We established B6-based immunodeficient strains harboring NOD-Sirpa (BRGS) which showed efficient human cell engraftment comparable to that of NOD -background strains. Consequently, BRGS mice are free from NOD-related abnormalities. This simplified strain should be useful in future xenotransplant study of cancer stem cells.