Erythropoiesis, but not thrombocytopoiesis, is affected by the presence of a large amount of subcutaneously implanted bone marrow.

The concept that megakaryocytopoiesis is regulated in part by the number of megakaryocytes themselves, separately from its regulation by the number of platelets, is referred to as autoregulation. Its occurrence has been implied from animal models that demonstrate compensated megakaryocytopenia. In that condition, normal platelet production can occur even though numbers of megakaryocytes are substantially reduced, and individual megakaryocytes exhibit changes consistent with their being stimulated. The present experiments were undertaken to determine whether the converse situation, namely suppression of megakaryocytopoiesis by an excess of megakaryocytes, could be created. The experimental model consisted of C57Bl mice in which as many as 10 isogeneic femurs were implanted subcutaneously 10 weeks before analysis. The implanted femurs contained hematopoietic marrow morphologically. They incorporated radioiron, but only about 40% as much as an equal number of normal femurs, so hematopoiesis did not regenerate to the full potential of the implanted marrows. After implantation of nine or 10 femurs, thrombocytopoiesis was normal as judged by platelet counts, mean platelet volumes, numbers of megakaryocytes in tibial marrow, and megakaryocyte sizes. Hematocrits were increased, but plasma erythropoietin levels were normal. The implants showed a 15- to 20-hour incorporation of radioiron of 9.4 +/- 0.5%. Iron incorporation into endogenous bones and spleen was reduced, demonstrating that erythropoiesis was redistributed. The total incorporation of iron into all hematopoietic tissue was slightly increased, but red-cell iron incorporation was normal, implying that there was more ineffective erythropoiesis than normal. Leukocyte counts, differentials, and tibial cellularity were normal. After implantation of three or six femurs, no abnormalities of hematopoiesis were detected, even though the implants incorporated iron in proportion to their number. Thus, erythropoiesis was adjusted by the excess of total marrow caused by nine or 10 subcutaneously implanted femurs. This is about the maximum of implanted marrow that is feasible with this model, and the failure to observe suppression of megakaryocytopoiesis may have been due to an inability to achieve a large enough number of megakaryocytes to elicit a detectable response. Alternatively, autoregulation of megakaryocytes may depend more on the marrow concentration of megakaryocytes than on the total body content.