Patterns of organ-specific engraftment by stem cell subsets and committed progenitors

The kinetics of blood and organ engraftment following transplants of defined populations of hematopoietic stem/progenitor cells were investigated utilizing cell populations defined by surface antigen and rhodamine-123 staining. While long-term repopulating stem cells, short-term multipotent progenitors and committed progenitors all reconstituted peripheral blood red cells and splenic cellularity, only the population of cells that includes highly enriched long-term repopulating stem cells (Thy-1.1lowLinnegSca-1+Rh123low) reconstituted marrow cellularity. In addition, peripheral blood platelet and nucleated cell count increased only after transplant of the long-term repopulating population. These results argue that the major cell population that functions to reconstitute hematopoiesis after bone marrow transplantation is a primitive, marrow-homing stem cell. Transplantation of highly enriched multipotent progenitors that lack long-term reconstituting potential had no impact on hematopoietic recovery, apart from a transient increase in circulating erythrocytes. These results suggest that the primary cell population that functions to reconstitute hematopoiesis in a transplant setting is the long-term repopulating stem cell. This observation is discussed in the context of the normal hematopoietic process.