beta 2 microglobulin-deficient (B2m(null)) NOD/SCID mice are excellent recipients for studying human stem cell function

Human SCID repopulating cells (SRC) are defined based on their functional a bility to repopulate the bone marrow of NODI SCID mice with both myeloid an d lymphoid cell populations. The frequency of SRC in umbilical cord blood c ells is 1 in 9.3 x 10(5) mononuclear cells. We report that as few as 8 x 10 (4) human cord blood mononuclear cells transplanted into NOD/SCID/B2m(null) mice resulted in mutlilineage differentiation in the murine bone marrow, r evealing a more than 11-fold higher SRC frequency than in NOD/SCID mice. Mo reover, as few as 2 to 5 x 10(3) CD34(+) cells recovered from the bone marr ow of primary transplanted NODI SCID mice were sufficient for engrafting se condary NOD/SCID/B2m(null) mice with SRC, suggesting SRC self-renewal. Thus , by using NOD/SCID/B2m(null) mice as recipients, we established a function al assay for human stem cells capable of engrafting the bone marrow of prim ary and secondary transplanted immune-deficient mice with SRC, providing a model that better resembles autologous stem cell transplantation. (C) 2000 by The American Society of Hematology.