| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Research Abstract |
Cancer stem cells (CSCs) are therapeutic targets and must be eliminated to cure the patients. However, those cells have not been found yet in myelodysplastic syndrome (MDS). Immunodeficient mice are widely used to reconstitute human hematopoiesis by xenotransplantation of hematopoietic stem cells (HSCs), and this model provides a powerful tool to evaluate biological properties of human cancer stem cells. We found that in xenograft rejection, the innate phagocytic reaction of mouse macrophages could occur because murine SIRPA (mSIRPA) on macrophages cannot bind to human CD47 (hCD47). Thus, introduction of human SIRPA allows mouse macrophage to bind hCD47 on the graft, resulting in inhibition of phagocytic reaction against human cells. Here, we have established a new immunodeficient mouse line, B6-Rag2(null)Il2rg(null) mice with human SIRPA to induce complete macrophage tolerance.This strain should be very useful in xenotransplant experiments to assay MDS stem cells.
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