Human marrow cd34+ and cd34+cd38- cells generate high levels of human hematofoiesis in lmmunodeficient mice

Human bone marrow (BM) cells have been shown to engraft in immunodeficient mice. To determine whether engraftment derived from item cells and/or from more mature populations, we have transplanted adult human hematopoietic marrow populations enriched for stem cells. Sublethally irradiated NOD/LtSz seid/seid mice received human hematopoietic marrow cells intravenously, followed by intraperitoneal injections of recombinant human hematopoietic growth factors (rfaSCF, rhIL-3, rhGM-CSF and rhG-CSF) 3 times per week. Stem cell-enriched (purified CD34⁺ and CD34⁺CD38-) and total mononuclear cell populations were transplanted in separate experiments. One, 2 or 3 months after transplantation the mice were sacrificed, and cells were taken from BM, spleen and thymus. Row cytometric analysis IQQ-4 using murine monoclonal antibodies against g human leukocyte differentiation antigens was " n employed to quantify the frequencies of total human cells and the different hematopoietic lineages. PCR amplification of a specific human sequence and colony-forming assays confirmed hematopoietic cells were detected at all timepoints tested (figure). Human erythroid. myeloid and B-lymphoid cells were present. In addition, there was an expansion in pay 30 Day 60 DayJK) the number of CD34 cells. Thus, purified CD34+ CD34⁺CD38' provided long-term MONONUCLEAR CELLS muitilineage human engraftment, supporting the D34-t- CELLS hypothesis that adult human marrow stem cells CD34-.CD38-CELLS inthis system.