Effects of recombinant erythropoietin on the concentration and cycling status of human marrow hematopoietic progenitor cells in vivo

Abstract

The concentration of human marrow progenitors CFU-E, BFU-E, CFU-GM, and CFU-Mk and the percentage of these progenitor cells in DNA synthesis were studied in nine patients with transfusion-dependent anemia of end- stage renal failure before and 2 weeks after treatment with human recombinant erythropoietin (Epo) at a dose of 150 to 300 U/kg intravenously three times per week. The concentration of CFU-E in the posttreatment marrow increased by a mean of 4.15-fold, BFU-E by 3.37- fold, CFU-GM by 1.86-fold, and CFU-Mk by 1.96-fold as compared with their respective concentrations in the pretreatment marrows. This increase in the concentrations of marrow progenitors was accompanied by almost a doubling of the percentage of these cells in DNA synthesis as assessed by the 3H-thymidine suicide technique. These observations demonstrate that at the progenitor cell level the human marrow responds to therapeutic doses of Epo as an organ rather than by a selective expansion of the erythroid cell line.

The Acute Effect of Intravenously Administered Recombinant Human Erythropoietin on the Immune Response of Uremic Patients Maintained on Regular Hemodialysis

“…Also, the absolute neutrophil count was significantly increased, a finding that was supported by Ganser and his co‐workers ( 17) who reported an increase in the number and size of CFU‐GM and colony forming unit‐granulocyte, erythrocyte, monocyte, and megakaryocyte (CFU‐GEMM). Also, Dessypris and his co‐workers ( 14) found similar results. The absolute number of lymphocytes in our work was also increased significantly.…”

“…Other reports suggest that in addition to its effect on CFU‐E, rhEPO stimulates the CFU‐mix and CFU‐granulocyte macrophage (GM) ( 14) leading to increased production of granulocytes, macrophages, and pleuripotential progenitors of the myeloid and monocyte lineage ( 15.) In 1987 Stutz et al.…”

Review article: thrombocytopenia in chronic liver disease and pharmacologic treatment options

“…Noteworthy, this domain is the one that binds to the c‐Mpl receptor and is adequate for signalling and supporting cellular proliferation (Figure 2). Although in vitro EPO does not seem to have a direct effect on megakaryocyte production or maturation without TPO‐co‐stimulation, in vivo EPO treatment caused an increase in circulating megakaryocytic progenitor cells, 92 and the EPO receptor is also expressed on megakaryocytes 93 …”

Erythropoietin increases platelet reactivity and platelet counts in patients with alcoholic liver cirrhosis: a randomized, double‐blind, placebo‐controlled study

“…In vivo , erythropoietin increased the number of megacaryocytes in the bone marrow of splenectomized mice 21 and elevated platelet counts in these mice 21 and in rats 22 . In patients with uraemia, erythropoietin treatment caused an increase in circulating bone marrow progenitor cells, including megakaryocytic progenitor cells, 23 thereby demonstrating an effect on a broad spectrum of human haematopoietic progenitor cells. Further, erythropoietin receptor is also expressed on megacaryocytes 24 …”