Behavior of Hematopoietic Stem Cells in a Large Animal

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 6; pp. 2031 - 2035
• Main Authors: Abkowitz, Janis L., Persik, Monica T., Shelton, Grady H., Ott, Richard L., Kiklevich, J. Veronika, Catlin, Sandra N., Guttorp, Peter
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 14-03-1995; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Bone marrow; Bone Marrow Transplantation - physiology; Cats; Colony-Forming Units Assay; Crosses, Genetic; Female; Glucosephosphate Dehydrogenase - analysis; Glucosephosphate Dehydrogenase - genetics; Granulocytes; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Hematopoietic stem cells; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Kinetics; Male; Medical research; Mice; Phenotype; Phenotypes; Progenitor cells; Species Specificity; Stem cells; Transplantation; Transplantation, Autologous; Transplants & implants; Wildcats
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.6.2031

To study the behavior of hematopoietic stem cells in vivo, we transplanted glucose-6-phosphate dehydrogenase (G6PD) heterozygous (female Safari) cats with small amounts of autologous marrow. The G6PD phenotypes of erythroid burst-forming units and granulocyte/macrophage colony-forming units were repeatedly assayed for 3.5-6 years after transplantation to track contributions of stem cell clones to the progenitor cell compartment. Two phases of stem cell kinetics were observed, which were similar to the pattern reported in comparable murine studies. Initially there were significant fluctuations in contributions of stem cell clones. Later clonal contributions to hematopoiesis stabilized. The initial phase of clonal disequilibrium, however, extended for 1-4.5 years (and not 2-6 months as seen in murine experiments). After this subsided, 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 hematopoietic 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 individual hematopoietic stem cell has a vast self-renewal and/or proliferative 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.