CD34+AC133+ cells isolated from cord blood are highly enriched in long-term culture-initiating cells, NOD/SCID-repopulating cells and dendritic cell progenitors

The AC133 antigen is a novel antigen selectively expressed on a subset of CD34(+) cells in human fetal liver, bone marrow, and blood as demonstrated by now cytometric analyses. In this study, we have further assessed the expression of AC133 on CD34(+) cells in hemopoietic samples and found that there was a highly significant difference between normal bone marrow and cord blood versus aphereses (p <0.0001) but not between bone marrow and cord blood. Most of the clonogenic cells (67%) were contained in the CD34(+)AC133(+) fraction. Compared with cultures of the CD34(+)AC133(-) cells, generation of progenitor cells in long-term culture on bone marrow stroma was consistently 10- to 100-fold higher in cultures initiated with CD34(+)AC133(+) cells and was maintained for the 8-10 weeks of culture. Only the CD34(+)AC133(+) cells were capable of repopulating NOD/SCID mice. Human cells were detectable as early as day 20, with increased levels (67%) apparent 40 days post-transplantation. Five thousand CD34(+)AC133(+) cells engrafted about 20% of the mice, while no engraftment was observed in animals transplanted with up to 1.2 x 10(5) CD34(+)AC133(-) cells. The CD34(+)AC133(+) population was also enriched (sevenfold) in dendritic cell precursors, and the dendritic cells generated were functionally active in a mixed lymphocyte reaction assay. AC133(+) cells should be useful in the study of cellular and molecular mechanisms regulating primitive hemopoietic cells.