Common Marmoset as a New Preclinical Animal Model for Human Gene Therapy of Hematological Disorders

Summary

For the purpose of secured and effective introduction of gene therapeutic approaches to human hematological disorders, we have been focusing on the common marmoset, a small non-human primates as a target preclinical animal for gene transfer. Here we characterize the common marmoset bone marrow (MBM) progenitor cells in vitro and investigate whether these cells respond to the human cytokines and are transduced by retrovirus vectors. Namely, we screened human cytokines (erythropoietin, granulocyte colony-stimulating factor (G-CSF), granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, IL-6, IL-11, stem cell factor (SCF), and thrombopoietin(TPO)) to examine their stimulating activities on MBM progenitor cells by colonogenic assay in methyl-cellulose. These human cytokines were demonstrated to have significant effects on MBM progenitor cells and stimulated the colony forming activity of each lineage dose-dependently. We then studied LacZ gene transfer efficiencies into MBM progenitor cells by retrovirus vector in the presence of human IL-3, IL-6 and SCE By using the mixed cell populations of MBM stromal cells and retrovirus producer cells, the transduction efficiency to CFU-GM (CFU-GEMM) increased significantly. Our results suggest that the marmoset would be useful as a preclinical animal to evaluate the effectiveness and safety of new gene therapy vector sytems for hematological disorders.