Multilineage hematopoietic development from umbilical cord blood cells with high aldehyde dehydrogenase activity

We have previously described the isolation of early hematopoietic progenitors based on their high expression of aldehyde dehydrogenase (ALDHbr cells; Proc. Nail. Acad. Sci. USA 91:9118). In those studies, the ALDH" cells isolated from umbilical cord blood (UCB) were highly enriched for CD34T CD38 cells and for early myeloid progenitors as monitored in long-term culture assays. We now report that the ALDH1" UCB cells contain high frequencies of NOD/SCID repopulating cells (SRC). In 5 of 6 mice transplanted with 3000 ALDH" UCB cells, human myeloid and B-lymphoid cells were evident in the marrow at 8 to 10 weeks post-transplant (median engraftment 13.8%; range 0.2 - 20.8%). The precise frequency of SRC within the ALDHbr UCB is currently being determined in limit dilution analyses. These data are supported by the in vitro development of myeloid (CD13', CD14 , and/or CD15), NK (CD56) and B (CD10VCD19) cells from CD34ALDHbI UCB cells when they were cultured in a variety of different long-term stromabased culture assay systems. In some assays, a 3- to 10-fold expansion of CD34+ cells was also noted over 5 to 6 weeks of culture in vitro. Small subfractions (typically 5-10%) of the ALDH" UCB are CD34 cells that can not be defined by any lineage-specific antigens. In contrast to the CD34ALDHhr UCB cells, the appropriate conditions to support the CD34 ALDHbI UCB in vitro have not yet been elucidated. In summary, our data suggest that the CD34ALDHbr UCB cells are multilineage hematopoietic progenitors while the CD34 ALDH1" UCB remain undefined.

Duke Scholars

Author Henry Elliot Rice Surgery, Pediatric General Surgery