Temporal thrombocytopenia after engraftment with defined stem cells with long-term marrow reconstituting activity

Delayed platelet recovery and altered marrow megakaryocytopoiesis was observed in highly irradiated mice following transplantation with 1000 lineage-negative, stem cell antigen-positive (Lin-Sca-1+) cells. Thirty days after transplantation, the mice were thrombocytopenic. Normal platelet levels were reestablished by 90 days after transplantation. Platelet levels were established from the bone marrow with altered megakaryocytopoiesis, however. Megakaryocyte progenitor numbers were found at reduced levels in the reconstituted marrow at all time points assessed. Bone marrow function was also different in that marrow reserve was also diminished. While the transplantation regime did give long-term reconstitution of blood cells, the quality of the marrow reserve was significantly impaired as revealed by response to further hematopoietic challenge. The data indicate that mice transplanted with a population of highly defined stem cells have perturbed marrow function, one characteristic being an altered process of megakaryocytopoiesis.