IDENTIFICATION OF HUMAN AND MOUSE HEMATOPOIETIC STEM-CELL POPULATIONSEXPRESSING HIGH-LEVELS OF MESSENGER-RNA ENCODING RETROVIRUS RECEPTORS

One obstacle to retrovirus-mediated gene therapy for human hematopoiet ic disorders is the low efficiency of gene transfer into pluripotent h ematopoietic stem cells (HSC). We have previously shown a direct corre lation between retrovirus receptor mRNA levels in mouse HSC and the ef ficiency with which they are transduced, In the present study, we assa yed retrovirus receptor mRNA levels in a variety of mouse and human HS C populations to identify HSC which may be more competent for retrovir us transduction, The highest levels of amphotropic retrovirus receptor (amphoR) mRNA were found in cryopreserved human cord blood HSC, The l evel of amphoR mRNA in Lin(-)CD34(+)CD38(-) cells isolated from frozen cord blood was 12-fold higher than the level in fresh cord blood Lin( -)CD34(+)CD38(-) cells. In mice, the level of amphoR mRNA in HSC from the bone marrow (BM) of mice treated with stem cell factor and granulo cyte-colony stimulating factor was 2.8- to 7.8-fold higher than in HSC from the BM of untreated mice, These findings suggest that HSC from f rozen cord blood and cytokine-mobilized BM may be superior targets for amphotropic retrovirus transduction compared with HSC from untreated adult BM, (C) 1998 by The American Society of Hematology.