Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-β2 microglobulin–null mice
H. Glimm, … , C. von Kalle, C.J. Eaves
H. Glimm, … , C. von Kalle, C.J. Eaves
Published January 15, 2001
Citation Information: J Clin Invest. 2001;107(2):199-206. https://doi.org/10.1172/JCI11519.
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Article

Previously undetected human hematopoietic cell populations with short-term repopulating activity selectively engraft NOD/SCID-β2 microglobulin–null mice

Abstract

Increasing use of purified or cultured human hematopoietic cells as transplants has revealed an urgent need for better methods to predict the speed and durability of their engraftment potential. We now show that NOD/SCID-β2 microglobulin–null (NOD/SCID-β2m–/–) mice are sequentially engrafted by two distinct and previously unrecognized populations of transplantable human short-term 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 broader 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-β2m–/– mice equally efficiently. In short-term expansion cultures of adult bone marrow cells, myeloid-restricted STRCs were preferentially amplified (greater than tenfold) and, interestingly, both types of STRC were found to be selectively elevated in mobilized peripheral blood harvests. These results suggest an enhanced sensitivity of STRCs to natural killer cell–mediated rejection. They also provide new in vivo assays for different types of human STRC that may help to predict the engraftment potential of clinical transplants and facilitate future investigation of early stages of human hematopoietic stem cell differentiation.

Authors

H. Glimm, W. Eisterer, K. Lee, J. Cashman, T.L. Holyoake, F. Nicolini, L.D. Shultz, C. von Kalle, C.J. Eaves

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Different engraftment kinetics of human cells in NOD/SCID-β2m–/– and NOD...
Different engraftment kinetics of human cells in NOD/SCID-β2m–/– and NOD/SCID mice. Groups of recipients were sacrificed 3, 6, and 13 weeks after transplantation, and the types and numbers of human cells present in the BM were determined by FACS analysis. (a) Total human CD45/71+ cells in NOD/SCID-β2m–/– mice (filled symbols, 13–14 mice/point) and NOD/SCID mice (open symbols, 15–16 mice/point) were calculated from data pooled from two independent experiments. (b) Absolute numbers of cells belonging to different human lineages present at different times. (c) Relative distribution of different types of human cells present after different periods in NOD/SCID-β2m–/– (filled bars) and NOD/SCID mice (open bars, same experiments as in b). Data for the 3-week NOD/SCID mice are not shown in this panel because of the low numbers of human cells present in these mice at this early time point. (d) Representative FACS profile of cells harvested from the BM of a NOD/SCID-β2m–/– mouse 3 weeks after transplantation of 2.5 × 105 human lin– BM cells. Note the high number of human erythroid (glycophorin A+) and megakaryocytic (CD41+) cells. Values for all figure parts are the mean ± SEM. ASignificant difference, P < 0.05.