SIMULATION OF HEMATOPOIESIS - IMPLICATIONS FOR THE GENE-THERAPY OF LYSOSOMAL-ENZYME DISORDERS

Although the hematopoietic stem cell is an attractive target for gene transfer, little is known about its biology in vivo in large animals ( including humans). We have studied the in vivo behavior of hematopoiet ic stem cells in glucose-6-phosphate dehydrogenase heterozygous (femal e Safari) cats, and demonstrated that clonal instability persists for up to 4.5 years after autologous marrow transplantation. This contrast s with the 2-6 months of clonal disequilibrium reported in comparable murine studies. Our data also suggest that hematopoietic stem cells do not self-renew more than once every 3 weeks. These data may have rele vance for strategies to optimize gene therapy in large animals and, by extension, in humans.