Gene transfer into fetal baboon hematopoietic progenitor cells

We studied hematopoietic progenitors from fetal baboon blood, marrow, and l iver at four time points (125, 140, 160, and 175 days) during the third tri mester (gestation similar to 180 days) to determine if fetal baboons might be an appropriate model for ia utero gene therapy of hematopoietic stem cel ls (HSCs). Cells were studied for expression of CD34, CD33, CD38, and HLA-D R, for progenitor content in colony-forming cell assays, and for susceptibi lity of CD34(+) progenitors to retrovirus-mediated gene transfer. Throughou t the third trimester, the frequency of CD34(+) progenitors in blood and ma rrow appears to remain unchanged at approximately 0.6 and 5.0%, respectivel y. In liver, progenitors progressively decrease to undetectable levels by d ay 175. The proportion of fetal baboon bone marrow and liver CD34(+) cells expressing CD38 and HLA-DR appears to increase with increasing fetal age, s imilar to changes reported for human cord blood CD34(+) cells. In fetal bab oon blood the proportion of CD34(+) cells expressing CD33 appears to decrea se with increasing gestational age, also similar to changes reported for hu man cord blood cells. Progenitors from human cord blood and baboon fetal ti ssues were similarly susceptible to transduction by the gibbon ape leukemia pseudotyped retroviral vector LAPSN(PG13) containing the genes for human p lacental alkaline phosphatase (AP) and the bacterial neomycin phosphotransf erase (neo). Fetal baboon and human hematopoietic progenitor cells undergo similar phenotypic changes during the third trimester of fetal development and are similarly susceptible to retrovirus-mediated gene transfer. The fet al baboon may be a model in which approaches to mobilization and gene trans fer into fetal HSCs can be studied.