Summary
Recombinant human erythropoietin (rhEpo), now available, might become increasingly more important for clinical use, e.g., in the treatment of anemia of chronic renal failure. As a prerequisite of clinical trials, we analyzed the stimulatory and suppressive effects of rhEpo on human hemopoiesis by adding rhEpo to in vitro cultures of nonadherent low-density bone marrow cells obtained from normal persons and from patients undergoing hemodialysis for chronic renal failure. rhEpo was shown to be an effective stimulus for erythroid and multilineage colony formation. The dose-response curve was similar for erythroid progenitors BFU-E from normal controls and patients with chronic renal failure. rhEpo had no effect on megakaryocytic colony formation nor on the megakaryocytic differentiation of multilineage stem cells. Because of a good stimulatory activity on erythroid and multilineage stem cells and lack of toxic effects, rhEpo might be useful in the treatment of certain kinds of anemia.
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Abbreviations
- BFU-E:
-
burst-forming unit-erythroid
- CFU-E:
-
colony forming unit-erythroid
- CFU-GEMM:
-
CFU-granulocyte, erythrocyte, macrophage, megakaryocyte
- CFU-GM:
-
CFU-granulocyte, macrophage
- CFU-Mk:
-
CFU-megakaryocyte
- IMDM:
-
Iscove's modified Dulbecco's medium
- Mo-CM:
-
Mo-cell line conditioned medium
- rhEpo:
-
recombinant human erythropoietin
References
Bommer J, Müller-Bühl E, Ritz E, Eifert J (1987) Recombinant human erythropoietin in anaemic patients on haemodialysis. Lancet I:392
Dessypris EN, Gleaton JH, Armstrong OL (1987) Effect of human recombinant erythropoietin on human marrow megakaryocyte colony formation in vitro. Br J Haematol 65:265–269
Dukes PP, Egrie JC, Strickland TW, Browne JK, Lin FK (1986) Megakaryocyte colony stimulating activity of recombinant human and monkey erythropoietin. In: Levine RF, Williams N, Levin J, Evatt BL (eds) Megakaryocyte development and function. AR Liss, New York, pp 105–109
Egrie JC, Strickland TW, Lane J, Aoki K, Cohen AM, Smalling R, Trail G, Lin FK, Browne JK, Hines DK (1986) Characterization and biological effects of recombinant human erythropoietin. Immunobiol 172:213–224
Eschbach JW, Egrie JC, Downing MR, Browne JK, Adamson JW (1987) Correction of anemia of end-stage renal disease with recombinant human erythropoietin: results of a combined phase I and II clinical trial. N Engl J Med 316:73–78
Fauser AA, Messner HA (1978) Granuloerythropoietic colonies in human bone marrow, peripheral blood and cord blood. Blood 52:1243–1248
Ganser A, Elstner E, Hoelzer D (1985) Megakaryocytic cells in mixed haemopoietic colonies (CFU-GEMM) from the peripheral blood of normal individuals. Br J Haematol 59:627–633
Golde DW, Quan SG, Cline MJ (1978) Human T lymphocyte cell line producing colony-stimulating activity. Blood 52:1068–1072
Graber SE, Krantz SB (1978) Erythropoietin and the control of red blood cell production. Ann Rev Med 29:51–66
Ishibashi T, Koziol JA, Burstein SA (1987) Human recombinant erythropoietin promotes differentiation of murine megakaryocytes in vitro. J Clin Invest 79:286–289
Jacobs K, Shoemaker C, Rudersdorf R, Neill SD, Kaufman RJ, Mufson A, Seehra J, Jones SS, Hewick R, Fritsch EF, Kawakita M, Shimizu T, Miyake T (1985) Isolation and characterization of genome and cDNA clones of human erythropoietin. Nature 313:306–310
Koike K, Shimizu T, Miyake T, Ihle JN, Ogawa M (1986) Hemopoietic colony formation by mouse spleen cells in serum-free culture supported by purified erythropoietin and/or interleukin 3. In: Levine RF, Williams N, Levin J, Evatt BL (eds) Megakaryocyte development and function. AR Liss, New York, pp 33–49
Lin FK, Suggs S, Lin CH et al. (1985) Cloning and expression of the human erythropoietin gene. Proc Natl Acad Sci, USA 82:7580–7584
Messner HA, Jamal N, Izaguirre C (1982) The growth of large megakaryocyte colonies from human bone marrow. J Cell Physiol [Suppl 1]:45–51
Mizoguchi H, Fujiwara Y, Sasaki R, Chiba H (1986) The effect of interleukin-3 and erythropoietin on murine megakaryocyte colony formation. In: Levine RF, Williams N, Levine J, Evatt BL (eds) Megakaryocyte development and function. AR Liss, New York, pp 111–115
Sawada K, Krantz SB, Kans JS, Dessypris EN, Sawyer S, Glick AD, Civin CI (1987) Purification of human erythroid colony-forming units and demonstration of specific binding of erythorpoietin. J Clin Invest 80:357–366
Sieff CA, Emerson SG, Mufson A, Gesner TG, Nathan DG (1986) Dependence of highly enriched human bone marrow progenitors on hemopoietic growth factors and their response to recombinant erythropoietin. J Clin Invest 77:74–81
Tetteroo PAT, Lansdorp PM, Leeksma OC, von dem Borne AEGKr (1983) Monoclonal antibodies against human platelet glycoprotein IIIa. Br J Haematol 55:509–522
Williams N, Jackson H, Iscove NN, Dukes PP (1984) The role of erythropoietin, thrombopoietic stimulating factor, and myeloid colony-stimulating factors on murine megakaryocyte colony formation. Exp Hematol 12:734–740
Winearls CG, Oliver DO, Pippard MJ, Reid C, Downing MR, Cotes PM (1986) Effect of human erythropoietin derived from recombinant DNA on the anaemia of patients maintained by chronic haemodialysis. Lancet II:1175–1178
Van Zant G, Goldwasser E (1979) Competition between erythropoietin and colony stimulating factor for target cells in mouse bone marrow. Blood 53:946–965
Zins B, Drüeke T, Zingraffe J, Bererhi L, Kreis H, Naret C, Delors S, Castaigne JP, Peterlongo F, Casadevall N, Varet B (1986) Erythropoietin treatment in anaemic patients on haemodialysis. Lancet II:1329
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Ganser, A., Völkers, B., Scigalla, P. et al. Effect of human recombinant erythropoietin on human hemopoietic progenitor cells in vitro. Klin Wochenschr 66, 236–240 (1988). https://doi.org/10.1007/BF01748162
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DOI: https://doi.org/10.1007/BF01748162