In vivo evaluation of candidate stem cell populations has traditionally utilized either lethal irradiation experiments or SCID/NOD-mice. To explore alternatives in a model that could examine both human and monkey cells, we have developed a fetal chimera model. First trimester, immune incompetent rhesus fetuses have been transplanted with human CD34+ cells by ultrasound guided intraperitoneal injection. On evaluation at birth and during the first 12 months of life, we have demonstrated persistent chimerism of human hematopoietic cells Chimerism is highest in the bone marrow (5-10% of CD34+ cells are of human phenotype). Chimerism in the peripheral blood varies between mononuclear fractions from 0.1-4%. However, the majority of human CD34+ cells in the bone marrow are apoptotic. This may explain the discordant level of engraftment in the bone marrow as compared to the peripheral blood. We have further determined that the administration of recombinant human granulocyte colony stimulating factor (G-CSF) for 10 days efficiently mobilizes human cells into the peripheral circulation. We observed an approximate 10-15% increase in human cells in both bone marrow and peripheral blood after G-CSF. These studies continue in an attempt to optimise the model and determine the in vivo engraftment characteristics of various hematopoietic progenitor subsets. Establishment of this model should prove useful in characterizing novel populations of human hematopoietic stem cells.
Showing the most recent 10 out of 365 publications
