PRIMITIVE HUMAN HEMATOPOIETIC-CELLS ARE ENRICHED IN CORD-BLOOD COMPARED WITH ADULT BONE-MARROW OR MOBILIZED PERIPHERAL-BLOOD AS MEASURED BYTHE QUANTITATIVE IN-VIVO SCID-REPOPULATING CELL ASSAY

We have previously reported the development of in vivo functional assa ys for primitive human hematopoietic cells based on their ability to r epopulate the bone marrow (BM) of severe combined immunodeficient (SCI D) and nonobese diabetic/SCID (NOD/SCID) mice following intravenous tr ansplantation, Accumulated data from gene marking and cell purificatio n experiments indicate that the engrafting cells (defined as SCID-repo pulating cells or SRC) are biologically distinct from and more primiti ve than most cells that can be assayed in vitro, Here we demonstrate t hrough limiting dilution analysis that the NOD/SCID xenotransplant mod el provides a quantitative assay for SRC, Using this assay, the freque ncy of SRC in cord blood (CB) was found to be 1 9.3 x 10(5) cells, Thi s was significantly higher than the frequency of 1 SRC in 3.0 x 10(6) adult BM cells or 1 in 6.0 x 10(6) mobilized peripheral blood (PB) cel ls from normal donors, Mice transplanted with limiting numbers of SRC were engrafted with both lymphoid and multilineage myeloid human cells , This functional assay is currently the only available method for qua ntitative analysis of human hematopoietic cells with repopulating capa city. Both CB and mobilized PB are increasingly being used as alternat ive sources of hematopoietic stem cells in allogeneic transplantation, Thus, the findings reported here will have important clinical as well as biologic implications. (C) 1997 by The American Society of Hematol ogy.