High marrow seeding efficiency of human lymphomyeloid repopulating cells in irradiated NOD/SCID mice

Transplantable human hematopoietic stem cells (competitive repopulating uni ts [CRU]) can be quantitated based on their ability to produce large popula tions of lymphoid and myeloid progeny within 6 weeks in the marrow of intra venously injected, sublethally irradiated NOD/SCID mice. It is shown that t he proportions of total injected human fetal liver and cord blood CRU in th e marrow of mice 24 hours after transplantation are 5% and 7%, respectively , as determined by limiting-dilution assays in other primary and secondary NOD/SCID mice. The similarity in these 2 seeding efficiency values suggests that mechanisms regulating the ability of human hematopoietic stem cells t o enter the marrow from the blood, at least in this xenotransplant model, d o not change between fetal life and birth, in addition, it appears that pre viously reported human stem cell frequencies and their in vivo self-renewal activity measured in NOD/SCID mice have been markedly underestimated. (C) 2000 by The American Society of Hematology.