NOD/SCID repopulating cells but not LTC-IC are enriched in human CD34(+) cells expressing the CCR1 chemokine receptor

Human haemopoietic stem and progenitor cells may he distinguished by the pa ttern of cell surface markers they display. The cells defined as 'stem' cel ls are heterogeneous and lack specific markers for their detection. However , they may be identified in in vitro assays such as the long-term culture i nitiating cell (LTC-LC) and in transplant assays involving immunosuppressed NOD/SCID mice. It is still not clear to what extent, if any, these cell po pulations overlap. The chemokine macrophage inflammatory protein-1 alpha (M lP-1 alpha) prolongs survival of LTC-IC in suspension cultures and we now s how that in longterm bone marrow cultures (LTBMC) maintenance of haemopoies is was significantly better from the CD34(+) cells which possess MIP-la rec eptors (P < 0.006). We examined one MIP-1 alpha receptor, CCR1, which is pr esent on CD34+ cells from haemopoietic tissues, In LTBMC the production of GM-CFC from CD34(+)CCR1(-) cells was significantly higher (P < 0.02) than t hat from CD34(+)CCR1(+) cultures and the incidence of LTC-IC was 3-to B-fol d higher in the CD34(+)CCR1(-) cell fraction. In contrast, the cells respon sible for high levels of engraftment in NOD/SCID mice were contained in the CD34(+)CCR1(+) cell fraction. The CD34(+)CCR1(+) cells engrafted to high l evels in NOD/SCID and generated large numbers of progenitor cells. Therefor e, we conclude that LTC-1C and SRC may be distinguished on the basis of exp ression of the chemokine receptor CCR1.