No abstract

The continuous administration of tridated thymidine (³H-TdR) into pregnant rats resulted in a complete labelling of cell nuclei in the offspring. Further injections with ³H-TdR for 6 weeks maintained the 100-percent labelling. Six weeks after the last ³H-TdR application, only cytokinetically resting cells were selectively labelled in the bone marrow of these animals. These comprised reticular cells, endothelial cells and 5% of the bone marrow lymphocyte population. In these animals a standardised amount of the marrow of both the femora was removed by mechanical means. In the undepleted part of the femur a stimulation of formerly cytokinetically resting cells could be observed. There was no indication of stimulation in distant bone marrow parts. In an additional experiment in which a single injection of ³H-TdR was given at various intervals after depletion, the above findings were supported by a high uptake of ³H-TdR in the stroma cells of the bone marrow. The findings indicate that repopulation of bone marrow stroma cells is a necessary process for a restoration of haemopoiesis.

A 34‐year‐old male patient with acute myeloid leukaemia, who showed an exponential increase in blood leukocyte count during a second relapse despite intensive cytostatic therapy, was treated by leukopheresis using an IBM continuous blood cell separator. The rapid growth of cells was arrested and the patient thereafter responded to cytostatic therapy. Investigation of cell kinetics using 3H‐TdR in vivo just before the cen‐trifugation treatment showed that in spite of leukopheresis, which removed a total of 5 times 1012 cells, 3H‐TdR labelled leukaemic blast cells were observable in the peripheral blood as long as 42 d after injection, having presumably ‘become quiescent. An increase during leukopheresis in the mitotic index of blast cells in the bone marrow and in the labelling index of blast cells in the blood after in vitro incubation with 14C‐TdR led to the deduction that a feedback mechanism was acting within the leukaemic blast cell population.

Inbred Lewis rats were labelled with (3H‐thymidine (3H‐TdR) in utero and for 6 weeks after birth to obtain 100 % labelling of all the cells in the animals. 6 weeks after the last 3H‐TdR injection only cytokinetically resting cells were still labelled. These cells comprised of two types of reticular cells, endothelial cells and a small fraction of bone marrow ‘lymphocytes’. At this time the animals were treated with 4 × 500 mg/kg body weight hydroxyurea at 6 hrs intervals. A profound marrow hypoplasia was obvious 6 hrs after the last HU injection. All proliferating precursor cells of the bone marrow were destroyed, whereas the cytokinetically resting cells were not changed in their absolute number. Successful transplantation of the marrow treated with HU to 1200 R X‐irradiated recipients provided evidence for the presence of ‘stem cells’ in the bone marrow of the donors and indicated that in rats bone marrow regeneration can be achieved in the absence of cells morphologically defined as haemocytoblasts.