BEHAVIOR OF HEMATOPOIETIC STEM-CELLS IN A LARGE ANIMAL

To study the behavior of hematopoietic stem cells in vivo, we transpla nted glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Saf ari) cats with small amounts of autologous marrow. The G6PD phenotypes of erythroid burst-forming units and granulocyte/macrophage colony-fo rming units were repeatedly assayed for 3.5-6 years after transplantat ion to track contributions of stem cell clones to the progenitor cell compartment. Two phases of stem cell kinetics were observed, which wer e similar to the pattern reported in comparable murine studies. Initia lly there were significant fluctuations in contributions of stem cell clones. Later clonal contributions to hematopoiesis stabilized. The in itial phase of conal disequilibrium, however, extended for 1-4.5 years (and not 2-6 months as seen in murine experiments). After this subsid ed, all progenitor cells from some animals expressed a single parental G6PD phenotype, suggesting that blood cell production could be stably maintained by the progeny of one (or a few) cells. As the hematopoiet ic demand of a cat (i.e., number of blood cells produced per lifetime) is over 600 times that of a mouse, this provides evidence that an ind ividual hematopoietic stem cell has a vast self-renewal and/or prolife rative capacity. The long phase of clonal instability may reflect the time required for stem cells to replicate sufficiently to reconstitute a large stem cell reserve.