Properties of haematopoietic stem cells surviving 5-fluorouracil treatment: evidence for a pre-CFU-S cell?

Abstract

The spleen colony assay of Till and McCulloch1, which is a clonal assay2, is considered to be a measure of the stem cell content of haematopoietic tissue. Stem cells are a heterogeneous population3–6 with respect to their capacity to generate further stem cells (assayed as colony-forming units in spleen, CFU-S) and progenitors of red cells, granulocytes, macrophages and platelets. It has been suggested that stem cells are organised for use according to their generation age5,6. There is evidence to indicate that drugs such as hydroxyurea (HU) and 5-fluorouracil (5-FU), which preferentially eliminate proliferating cells, spare non-cycling stem cells which have a high capacity to generate other stem cells6 and progenitors of granulocytes and macrophages6 as well as megakaryocytes7. We show here, however, that the CFU-S content of haematopoietic tissue is not an adequate predictor of the capacity of that tissue to repopulate bone marrow of a lethally irradiated host. Furthermore it appears that haematopoietic stem cells are not only heterogeneous with respect to their capacity to generate other stem cells and progenitors of haemic cells in the spleen but also differ in their capacity to ‘home’ to either the bone marrow or spleen. The evidence suggests a class of ‘primitive’ haematopoietic stem cell (pre-CFU-S) that accumulates in the bone marrow to give rise to cells capable of growing in spleen.