Cancer stem cell assay by a new immunodeficient mouse model harboring a complete macrophage tolerance

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659463
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Hematology
• Research Institution: Kyushu University
• Principal Investigator: AKASHI KOICHI 九州大学, 医学(系)研究科(研究院), 教授 (80380385)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: がん幹細胞 / 異種移植アッセイ / マクロファージ / SIRPA

Outline of Final Research Achievements

To evaluate human cancer stem cells in xenotransplant models, a variety of immunodeficient mouse lines have been developed. We found that in xenograft engraftment, inhibition of phagocytic reaction of mouse macrophages is essential in addition to lymphoid depletion. Murine signal regulatory protein alpha (mSIRPA) on macrophages cannot bind to human CD47 (hCD47), resulting phagocytic reaction against human cells. Here, we have established a new immunodeficient BRGhS mouse line, B6.Rag2(null)Il2rg(null), harboring a complete macrophage tolerance. BRGhS mouse line was introduced by human SIRPA, which allows to bind human CD47, resulting in inhibition of phagocytosis against human cell graft. BRGhS strain should be very useful in future xenotransplant experiments of human cancer stem cells.

Free Research Field

血液内科