The biology of long-term bone marrow cultures and its application to bone marrow transplantation

Long-term bone marrow cultures have been applied to the study and to the treatment of hemopoietic disease. The incidence of murine primitive (stem) cells with the ability to repopulate irradiated bone morrow stroma is similar to that of cells able to repopulate the hemopoietic system of potentially lethally irradiated mice. In human bone marrow, cells with in vitro repopulating ability have been estimated as 0.5% to 1% of the CD34+ cells. The increase in primitive cells in the circulation seen after administration of growth factors has been exploited by harvesting those cells for use together with bone marrow in autologous transplants. The ability of primitive cells (harvested after granulocyte colony-stimulating factor plus chemotherapy) to reconstitute irradiated marrow stromas indicates that their repopulation capacity in vitro is at least as good as that of bone marrow. This is confirmed by experimental data in mice showing that small volumes of peripheral blood (after granulocyte colony-stimulating factor administration) are capable of long-term repopulation. The regulator capacity of marrow stroma has been exploited to purge bone marrow cultures from patients with acute myeloblastic leukemia in first remission and from treated patients with chronic myelogenous leukemia before using the cultured cells for autologous transplant. The results to date, although preliminary, indicate a role for this methodology in the treatment of leukemia.