β2 Microglobulin-deficient (B2mnull) NOD/SCID mice are excellent recipients for studying human stem cell function

Abstract

Abstract Human SCID repopulating cells (SRC) are defined based on their functional ability to repopulate the bone marrow of NOD/SCID mice with both myeloid and lymphoid cell populations. The frequency of SRC in umbilical cord blood cells is 1 in 9.3 × 105mononuclear cells. We report that as few as 8 × 104 human cord blood mononuclear cells transplanted into NOD/SCID/B2mnull mice resulted in mutlilineage differentiation in the murine bone marrow, revealing a more than 11-fold higher SRC frequency than in NOD/SCID mice. Moreover, as few as 2 to 5 × 103 CD34+ cells recovered from the bone marrow of primary transplanted NOD/SCID mice were sufficient for engrafting secondary NOD/SCID/B2mnull mice with SRC, suggesting SRC self-renewal. Thus, by using NOD/SCID/B2mnull mice as recipients, we established a functional assay for human stem cells capable of engrafting the bone marrow of primary and secondary transplanted immune-deficient mice with SRC, providing a model that better resembles autologous stem cell transplantation.