Skip to main content
The Yale Journal of Biology and Medicine logoLink to The Yale Journal of Biology and Medicine
. 1990 Sep-Oct;63(5):411–418.

Numerous growth factors can influence in vitro megakaryocytopoiesis.

R Hoffman 1, R Briddell 1, E Bruno 1
PMCID: PMC2589366  PMID: 2293500

Abstract

At least two classes of human megakaryocyte progenitor cells have been identified: the burst-forming unit megakaryocyte (BFU-MK) and the colony-forming unit megakaryocyte (CFU-MK). The BFU-MK is the most primitive progenitor cell committed to the megakaryocytic lineage. The CFU-MK appears to be a more differentiated megakaryocyte progenitor cell and is thought to be ultimately a descendant of the BFU-MK. A number of recombinant cytokines have recently been shown to be able to promote megakaryocyte colony formation in vitro. Recombinant GM-CSF and IL-3, in particular, have the ability to promote both CFU-MK- and BFU-MK-derived colony stimulatory formation. The activities of these two cytokines on in vitro megakaryocytopoiesis are also additive. Recent results of clinical trials in both primates and humans, in which these glycoproteins were administered in vivo, suggest that these cytokines, both alone and in combination, can enhance in vivo thrombopoiesis and therefore may be potentially useful in the treatment of thrombocytopenic disorders.

Full text

PDF
411

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abe T., Fuhrer J. P., Bregman M. D., Kuramoto A., Murphy M. J., Jr Factors regulating megakaryocytopoiesis and platelet formation. Adv Exp Med Biol. 1988;241:183–190. doi: 10.1007/978-1-4684-5571-7_21. [DOI] [PubMed] [Google Scholar]
  2. Briddell R. A., Brandt J. E., Straneva J. E., Srour E. F., Hoffman R. Characterization of the human burst-forming unit-megakaryocyte. Blood. 1989 Jul;74(1):145–151. [PubMed] [Google Scholar]
  3. Bruno E., Briddell R., Hoffman R. Effect of recombinant and purified hematopoietic growth factors on human megakaryocyte colony formation. Exp Hematol. 1988 Jun;16(5):371–377. [PubMed] [Google Scholar]
  4. Bruno E., Hoffman R. Effect of interleukin 6 on in vitro human megakaryocytopoiesis: its interaction with other cytokines. Exp Hematol. 1989 Nov;17(10):1038–1043. [PubMed] [Google Scholar]
  5. Burstein S. A., Adamson J. W., Erb S. K., Harker L. A. Megakaryocytopoiesis in the mouse: response to varying platelet demand. J Cell Physiol. 1981 Nov;109(2):333–341. doi: 10.1002/jcp.1041090217. [DOI] [PubMed] [Google Scholar]
  6. Caracciolo D., Clark S. C., Rovera G. Human interleukin-6 supports granulocytic differentiation of hematopoietic progenitor cells and acts synergistically with GM-CSF. Blood. 1989 Feb 15;73(3):666–670. [PubMed] [Google Scholar]
  7. Donahue R. E., Wang E. A., Stone D. K., Kamen R., Wong G. G., Sehgal P. K., Nathan D. G., Clark S. C. Stimulation of haematopoiesis in primates by continuous infusion of recombinant human GM-CSF. 1986 Jun 26-Jul 2Nature. 321(6073):872–875. doi: 10.1038/321872a0. [DOI] [PubMed] [Google Scholar]
  8. Geissler D., Konwalinka G., Peschel C., Boyd J., Odavic R., Braunsteiner H. Clonal growth of human megakaryocytic progenitor cells in a micro-agar culture system: simultaneous proliferation of megakaryocytic, granulocytic, and erythroid progenitor cells (CFU-M, CFU-C, BFU-E) and T-lymphocytic colonies (CFU-TL). Int J Cell Cloning. 1983 Oct;1(5):377–388. doi: 10.1002/stem.5530010505. [DOI] [PubMed] [Google Scholar]
  9. Hill R. J., Levin J. Regulators of thrombopoiesis: their biochemistry and physiology. Blood Cells. 1989;15(1):141–166. [PubMed] [Google Scholar]
  10. Hill R. J., Warren M. K., Levin J. Stimulation of thrombopoiesis in mice by human recombinant interleukin 6. J Clin Invest. 1990 Apr;85(4):1242–1247. doi: 10.1172/JCI114559. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Hoffman R., Mazur E., Bruno E., Floyd V. Assay of an activity in the serum of patients with disorders of thrombopoiesis that stimulates formation of megakaryocytic colonies. N Engl J Med. 1981 Sep 3;305(10):533–538. doi: 10.1056/NEJM198109033051001. [DOI] [PubMed] [Google Scholar]
  12. Hoffman R. Regulation of megakaryocytopoiesis. Blood. 1989 Sep;74(4):1196–1212. [PubMed] [Google Scholar]
  13. Hoffman R., Yang H. H., Bruno E., Straneva J. E. Purification and partial characterization of a megakaryocyte colony-stimulating factor from human plasma. J Clin Invest. 1985 Apr;75(4):1174–1182. doi: 10.1172/JCI111813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Ikebuchi K., Wong G. G., Clark S. C., Ihle J. N., Hirai Y., Ogawa M. Interleukin 6 enhancement of interleukin 3-dependent proliferation of multipotential hemopoietic progenitors. Proc Natl Acad Sci U S A. 1987 Dec;84(24):9035–9039. doi: 10.1073/pnas.84.24.9035. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ishibashi T., Kimura H., Shikama Y., Uchida T., Kariyone S., Hirano T., Kishimoto T., Takatsuki F., Akiyama Y. Interleukin-6 is a potent thrombopoietic factor in vivo in mice. Blood. 1989 Sep;74(4):1241–1244. [PubMed] [Google Scholar]
  16. Ishibashi T., Kimura H., Uchida T., Kariyone S., Friese P., Burstein S. A. Human interleukin 6 is a direct promoter of maturation of megakaryocytes in vitro. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5953–5957. doi: 10.1073/pnas.86.15.5953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Kaushansky K., O'Hara P. J., Berkner K., Segal G. M., Hagen F. S., Adamson J. W. Genomic cloning, characterization, and multilineage growth-promoting activity of human granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1986 May;83(10):3101–3105. doi: 10.1073/pnas.83.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kawakita M., Enomoto K., Katayama N., Kishimoto S., Miyake T. Thrombopoiesis- and megakaryocyte colony-stimulating factors in the urine of patients with idiopathic thrombocytopenic purpura. Br J Haematol. 1981 Aug;48(4):609–615. doi: 10.1111/j.1365-2141.1981.00609.x. [DOI] [PubMed] [Google Scholar]
  19. Kawakita M., Ogawa M., Goldwasser E., Miyake T. Characterization of human megakaryocyte colony-stimulating factor in the urinary extracts from patients with aplastic anemia and idiopathic thrombocytopenic purpura. Blood. 1983 Mar;61(3):556–560. [PubMed] [Google Scholar]
  20. Kimura H., Burstein S. A., Thorning D., Powell J. S., Harker L. A., Fialkow P. J., Adamson J. W. Human megakaryocytic progenitors (CFU-M) assayed in methylcellulose: physical characteristics and requirements for growth. J Cell Physiol. 1984 Jan;118(1):87–96. doi: 10.1002/jcp.1041180115. [DOI] [PubMed] [Google Scholar]
  21. Koike K., Nakahata T., Takagi M., Kobayashi T., Ishiguro A., Tsuji K., Naganuma K., Okano A., Akiyama Y., Akabane T. Synergism of BSF-2/interleukin 6 and interleukin 3 on development of multipotential hemopoietic progenitors in serum-free culture. J Exp Med. 1988 Sep 1;168(3):879–890. doi: 10.1084/jem.168.3.879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kunimoto D. Y., Nordan R. P., Strober W. IL-6 is a potent cofactor of IL-1 in IgM synthesis and of IL-5 in IgA synthesis. J Immunol. 1989 Oct 1;143(7):2230–2235. [PubMed] [Google Scholar]
  23. Levin J., Levin F. C., Metcalf D. The effects of acute thrombocytopenia on megakaryocyte-CFC and granulocyte-macrophage-CFC in mice: studies of bone marrow and spleen. Blood. 1980 Aug;56(2):274–283. [PubMed] [Google Scholar]
  24. Long M. W., Gragowski L. L., Heffner C. H., Boxer L. A. Phorbol diesters stimulate the development of an early murine progenitor cell. The burst-forming unit-megakaryocyte. J Clin Invest. 1985 Aug;76(2):431–438. doi: 10.1172/JCI111990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Lopez A. F., To L. B., Yang Y. C., Gamble J. R., Shannon M. F., Burns G. F., Dyson P. G., Juttner C. A., Clark S., Vadas M. A. Stimulation of proliferation, differentiation, and function of human cells by primate interleukin 3. Proc Natl Acad Sci U S A. 1987 May;84(9):2761–2765. doi: 10.1073/pnas.84.9.2761. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lotem J., Shabo Y., Sachs L. Regulation of megakaryocyte development by interleukin-6. Blood. 1989 Oct;74(5):1545–1551. [PubMed] [Google Scholar]
  27. Mazur E. M., Cohen J. L., Wong G. G., Clark S. C. Modest stimulatory effect of recombinant human GM-CSF on colony growth from peripheral blood human megakaryocyte progenitor cells. Exp Hematol. 1987 Dec;15(11):1128–1133. [PubMed] [Google Scholar]
  28. Mazur E. M., Hoffman R., Chasis J., Marchesi S., Bruno E. Immunofluorescent identification of human megakaryocyte colonies using an antiplatelet glycoprotein antiserum. Blood. 1981 Feb;57(2):277–286. [PubMed] [Google Scholar]
  29. Mazur E. M. Megakaryocytopoiesis and platelet production: a review. Exp Hematol. 1987 May;15(4):340–350. [PubMed] [Google Scholar]
  30. Mazur E. M., South K. Human megakaryocyte colony-stimulating factor in sera from aplastic dogs: partial purification, characterization, and determination of hematopoietic cell lineage specificity. Exp Hematol. 1985 Dec;13(11):1164–1172. [PubMed] [Google Scholar]
  31. Mazur E. M., de Alarcón P., South K., Miceli L. Human serum megakaryocyte colony-stimulating activity increases in response to intensive cytotoxic chemotherapy. Exp Hematol. 1984 Sep;12(8):624–628. [PubMed] [Google Scholar]
  32. McDonald T. P. Thrombopoietin: its biology, purification, and characterization. Exp Hematol. 1988 Mar;16(3):201–205. [PubMed] [Google Scholar]
  33. McLeod D. L., Shreve M. M., Axelrad A. A. Induction of megakaryocyte colonies with platelet formation in vitro. Nature. 1976 Jun 10;261(5560):492–494. doi: 10.1038/261492a0. [DOI] [PubMed] [Google Scholar]
  34. Messner H. A., Jamal N., Izaguirre C. The growth of large megakaryocyte colonies from human bone marrow. J Cell Physiol Suppl. 1982;1:45–51. doi: 10.1002/jcp.1041130410. [DOI] [PubMed] [Google Scholar]
  35. Messner H. A., Yamasaki K., Jamal N., Minden M. M., Yang Y. C., Wong G. G., Clark S. C. Growth of human hemopoietic colonies in response to recombinant gibbon interleukin 3: comparison with human recombinant granulocyte and granulocyte-macrophage colony-stimulating factor. Proc Natl Acad Sci U S A. 1987 Oct;84(19):6765–6769. doi: 10.1073/pnas.84.19.6765. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Metcalf D., MacDonald H. R., Odartchenko N., Sordat B. Growth of mouse megakaryocyte colonies in vitro. Proc Natl Acad Sci U S A. 1975 May;72(5):1744–1748. doi: 10.1073/pnas.72.5.1744. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Miura M., Jackson C. W., Steward S. A. Increase in circulating megakaryocyte growth-promoting activity (Meg-GPA) following sublethal irradiation is not related to decreased platelets. Exp Hematol. 1988 Feb;16(2):139–144. [PubMed] [Google Scholar]
  38. Mizoguchi H., Fujiwara Y., Sasaki R., Chiba H. The effect of interleukin 3 and erythropoietin on murine megakaryocyte colony formation. Prog Clin Biol Res. 1986;215:111–115. [PubMed] [Google Scholar]
  39. Nakeff A., Daniels-McQueen S. In vitro colony assay for a new class of megakaryocyte precursor: colony-forming unit megakaryocyte (CFU-M). Proc Soc Exp Biol Med. 1976 Mar;151(3):587–590. doi: 10.3181/00379727-151-39265. [DOI] [PubMed] [Google Scholar]
  40. Paulus J. M., Prenant M., Deschamps J. F., Henry-Amar M. Polyploid megakaryocytes develop randomly from a multicompartmental system of committed progenitors. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4410–4414. doi: 10.1073/pnas.79.14.4410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Quesenberry P. J., Ihle J. N., McGrath E. The effect of interleukin 3 and GM-CSA-2 on megakaryocyte and myeloid clonal colony formation. Blood. 1985 Jan;65(1):214–217. [PubMed] [Google Scholar]
  42. Renauld J. C., Vink A., Van Snick J. Accessory signals in murine cytolytic T cell responses. Dual requirement for IL-1 and IL-6. J Immunol. 1989 Sep 15;143(6):1894–1898. [PubMed] [Google Scholar]
  43. Robinson B. E., McGrath H. E., Quesenberry P. J. Recombinant murine granulocyte macrophage colony-stimulating factor has megakaryocyte colony-stimulating activity and augments megakaryocyte colony stimulation by interleukin 3. J Clin Invest. 1987 Jun;79(6):1648–1652. doi: 10.1172/JCI113002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sakaguchi M., Kawakita M., Matsushita J., Shibuya K., Koishihara Y., Takatsuki K. Human erythropoietin stimulates murine megakaryopoiesis in serum-free culture. Exp Hematol. 1987 Nov;15(10):1028–1034. [PubMed] [Google Scholar]
  45. Sieff C. A., Niemeyer C. M., Nathan D. G., Ekern S. C., Bieber F. R., Yang Y. C., Wong G., Clark S. C. Stimulation of human hematopoietic colony formation by recombinant gibbon multi-colony-stimulating factor or interleukin 3. J Clin Invest. 1987 Sep;80(3):818–823. doi: 10.1172/JCI113139. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Solberg L. A., Jr, Jamal N., Messner H. A. Characterization of human megakaryocytic colony formation in human plasma. J Cell Physiol. 1985 Jul;124(1):67–74. doi: 10.1002/jcp.1041240112. [DOI] [PubMed] [Google Scholar]
  47. Teramura M., Katahira J., Hoshino S., Motoji T., Oshimi K., Mizoguchi H. Clonal growth of human megakaryocyte progenitors in serum-free cultures: effect of recombinant human interleukin 3. Exp Hematol. 1988 Nov;16(10):843–848. [PubMed] [Google Scholar]
  48. Teramura M., Katahira J., Hoshino S., Motoji T., Oshimi K., Mizoguchi H. Effect of recombinant hemopoietic growth factors on human megakaryocyte colony formation in serum-free cultures. Exp Hematol. 1989 Nov;17(10):1011–1016. [PubMed] [Google Scholar]
  49. Vainchenker W., Bouguet J., Guichard J., Breton-Gorius J. Megakaryocyte colony formation from human bone marrow precursors. Blood. 1979 Oct;54(4):940–945. [PubMed] [Google Scholar]
  50. Warren M. K., Conroy L. B., Rose J. S. The role of interleukin 6 and interleukin 1 in megakaryocyte development. Exp Hematol. 1989 Dec;17(11):1095–1099. [PubMed] [Google Scholar]
  51. Williams N., Eger R. R., Jackson H. M., Nelson D. J. Two-factor requirement for murine megakaryocyte colony formation. J Cell Physiol. 1982 Jan;110(1):101–104. doi: 10.1002/jcp.1041100116. [DOI] [PubMed] [Google Scholar]
  52. Wong G. G., Clark S. C. Multiple actions of interleukin 6 within a cytokine network. Immunol Today. 1988 May;9(5):137–139. doi: 10.1016/0167-5699(88)91200-5. [DOI] [PubMed] [Google Scholar]
  53. Wong G. G., Witek-Giannotti J. S., Temple P. A., Kriz R., Ferenz C., Hewick R. M., Clark S. C., Ikebuchi K., Ogawa M. Stimulation of murine hemopoietic colony formation by human IL-6. J Immunol. 1988 May 1;140(9):3040–3044. [PubMed] [Google Scholar]
  54. Yang H. H., Bruno E., Hoffman R. Studies of human megakaryocytopoiesis using an anti-megakaryocyte colony-stimulating factor antiserum. J Clin Invest. 1986 Jun;77(6):1873–1880. doi: 10.1172/JCI112514. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The Yale Journal of Biology and Medicine are provided here courtesy of Yale Journal of Biology and Medicine

RESOURCES