Rescue from lethal irradiation correlates with transplantation of 10-20 CFU-S-day 12.

Repopulation by donor cells of a bone marrow ablated by irradiation is now recognized to proceed in two phases: initial repopulation that may be temporary followed by permanent engraftment of longterm repopulating cells (LTRC). While a single LTRC has been shown to be capable of restoring the entire lymph-hemopoietic system of an irradiated animal, the identity of the temporary repopulating cells has not been established unequivocally. We used the results of transplantation of subpopulations successively enriched for LTRC and containing varying numbers of CFU-S-12 (colony-forming units in the spleen at day 12 post transplantation) and progenitors to determine the likely cell type and number of cells needed for initial survival after radiation.

Hematopoietic reserve provided by spleen colony-forming units (CFU-S).

Using quantitative data available from the literature on murine hematopoiesis, the functional reserve of multipotential stem cells was calculated by comparing daily blood cell production with the potential of clonogenic spleen colony-forming cells (CFU-S) to generate blood cells. The potential of the day-8 CFU-S (CFU-S-8) population is estimated to be from 4000 to 37,000 times greater than needed in steady-state hematopoiesis. The CFU-S population may thus serve to provide a functional reserve to supply large numbers of peripheral blood cells via committed lineage-specific cells within days, whenever needed.

Self-renewal of the long-term repopulating stem cell.

Self-renewal implies maintenance of all attributes of the original in the offspring and is considered characteristic of the hemopoietic stem cells. Yet, it has been questioned whether one of the most primitive hemopoietic stem cells, the long-term repopulating cell (LTRC), has that capacity. The present experiments demonstrate that single LTRCs can repopulate the lymphohemopoietic system of a lethally irradiated mouse and that the progeny of a single LTRC in a primary recipient again contains LTRCs capable of repopulating lethally irradiated secondary recipients.

Competitive repopulation in leukemic and normal bone marrow.

The success of chemotherapy in leukemias in which the marrow appears entirely replaced by leukemic cells must be due to the persistence of some normal stem cells. The implied competition between leukemic and normal stem cells is thus akin to the competition between donor and host cells in irradiated animals. A review of that competition points to the importance of the quantitative relationships between the competing stem cells, even when one of the competing stem cell clones has a proliferative advantage.