The variation of hematopoietic stem cell self-renewal capacity as a function of age: further evidence for heterogenicity of the stem cell compartment.

There is substantial evidence for limited proliferative capacity of the hematopoietic progenitors. Hematopoiesis in mice is maintained by primitive stem cells that are assayed by their ability to form spleen colonies (CFU-S). To measure the average proliferative capacity of these cells (CFU-S). bone marrow containing 50-1 50 CFU-S is injected into lethally irradiated mice. and 14 days later. the number present in the recipient marrow is measured. In fetal life between 1 3 and 1 6 days of gestation. the hematopoietic stem cells are primarily localized in the liver. There is a decrease in the average proliferative capacity of these stem cells as they progress from fetal life into adulthood. This proliferative capacity of these significantly increases in late adulthood. However. if one scores maximum selfrenewal or proliferative capacity by another assay consisting of the serial transplantation of marrow at 1 4-day