IDENTIFICATION OF PRIMITIVE HUMAN HEMATOPOIETIC-CELLS CAPABLE OF REPOPULATING NOD SCID MOUSE BONE-MARROW - IMPLICATIONS FOR GENE-THERAPY/

The development of stem-cell gene therapy is hindered by the absence o f repopulation assays for primitive human hematopoietic cells. Current methods of gene transfer rely on in vitro colony-forming cell (CFC) a nd long-term culture-initiating cell (LTC-IC) assays, as well as infer ence from other mammalian species. We have identified a novel human he matopoietic cell, the SCID-repopulating cell (SRC), a cell more primit ive than most LTC-ICs and CFCs. The SRC, exclusively present in the CD 4(+)CD8(-) fraction, is capable of multilineage repopulation of the bo ne marrow of nonobese diabetic mice with severe combined immunodeficie ncy disease (NOD/SCID mice). SRCs were rarely transduced with retrovir uses, distinguishing them from most CFCs and LTC-ICs. This observation is consistent with the low level of gene marking seen in human gene t herapy trials. An SRC assay may aid in the characterization of hematop oiesis, as well as the improvement of transduction methods.