CD34(-TERM CULTURE-INITIATING CELLS, NOD()AC133(+) CELLS ISOLATED FROM CORD BLOOD ARE HIGHLY ENRICHED IN LONG)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 demo nstrated by now cytometric analyses. In this study, we have further as sessed the expression of AC133 on CD34(+) cells in hemopoietic samples and found that there was a highly significant difference between norm al bone marrow and cord blood versus aphereses (p <0.0001) but not bet ween bone marrow and cord blood. Most of the clonogenic cells (67%) we re contained in the CD34(+)AC133(+) fraction. Compared with cultures o f the CD34(+)AC133(-) cells, generation of progenitor cells in long-te rm culture on bone marrow stroma was consistently 10- to 100-fold high er in cultures initiated with CD34(+)AC133(+) cells and was maintained for the 8-10 weeks of culture. Only the CD34(+)AC133(+) cells were ca pable of repopulating NOD/SCID mice. Human cells were detectable as ea rly as day 20, with increased levels (67%) apparent 40 days post-trans plantation. Five thousand CD34(+)AC133(+) cells engrafted about 20% of the mice, while no engraftment was observed in animals transplanted w ith up to 1.2 x 10(5) CD34(+)AC133(-) cells. The CD34(+)AC133(+) popul ation was also enriched (sevenfold) in dendritic cell precursors, and the dendritic cells generated were functionally active in a mixed lymp hocyte reaction assay. AC133(+) cells should be useful in the study of cellular and molecular mechanisms regulating primitive hemopoietic ce lls.