Previously undetected human hematopoietic cell populations with short-termrepopulating activity selectively engraft NOD/SCID-beta 2 microglobulin-null mice

Increasing use of purified or cultured human hematopoietic cells as transpl ants has revealed an urgent need for better methods to predict the speed an d durability of their engraftment potential. We now show that NOD/SCID-beta 2 microglobulin-null (NOD/SCID-beta 2m(-/-)) mice are sequentially engrafte d by two distinct and previously unrecognized populations of transplantable human shortterm repopulating hematopoietic cells (STRCs), neither of which efficiently engraft NOD/SCID mice, One is predominantly CD34(+)CD38(+) and is myeloid-restricted; the other is predominantly CD34(+)CD38(-) and has b roader lymphomyeloid differentiation potential. In contrast, the long-term repopulating human cells that generate lymphoid and myeloid progeny in NOD/ SCID mice engraft and self-renew in NOD/SCID-beta 2m(-/-) mice equally effi ciently. In short-term expansion cultures of adult bone marrow cells, myelo id-restricted STRCs were preferentially amplified (greater than tenfold) an d, interestingly, both types of STRC were found to be selectively elevated in mobilized peripheral blood harvests. These results suggest an enhanced s ensitivity of STRCs to natural killer cell-mediated rejection. They also pr ovide new in vivo assays for different types of human STRC that may help to predict the engraftment potential of clinical transplants and facilitate f uture investigation of early stages of human hematopoietic stem cell differ entiation.