hematopoietic cell growth factors


Summary: These growth factors comprise a family of hematopoietic regulators with biological specificities defined by their ability to support proliferation and differentiation of blood cells of different lineages. ERYTHROPOIETIN and the COLONY-STIMULATING FACTORS belong to this family. Some of these factors have been studied and used in the treatment of chemotherapy-induced neutropenia, myelodysplastic syndromes, and bone marrow failure syndromes.

Top Publications

  1. Hiraoka A, Sugimura A, Seki T, Nagasawa T, Ohta N, Shimonishi M, et al. Cloning, expression, and characterization of a cDNA encoding a novel human growth factor for primitive hematopoietic progenitor cells. Proc Natl Acad Sci U S A. 1997;94:7577-82 pubmed
    ..SCGF could disclose some human-specific mechanisms as yet unidentified from studies on the murine hematopoietic system. ..
  2. Hiraoka A, Yano Ki K, Kagami N, Takeshige K, Mio H, Anazawa H, et al. Stem cell growth factor: in situ hybridization analysis on the gene expression, molecular characterization and in vitro proliferative activity of a recombinant preparation on primitive hematopoietic progenitor cells. Hematol J. 2001;2:307-15 pubmed
    ..SCGF is selectively produced by osseous and hematopoietic stromal cells, and can mediate their proliferative activity on primitive hematopoietic progenitor cells. ..
  3. Hiraoka A. Leukemia cell lines require self-secreted stem cell growth factor (SCGF) for their proliferation. Leuk Res. 2008;32:1623-5 pubmed publisher
  4. Kawada H, Takizawa S, Takanashi T, Morita Y, Fujita J, Fukuda K, et al. Administration of hematopoietic cytokines in the subacute phase after cerebral infarction is effective for functional recovery facilitating proliferation of intrinsic neural stem/progenitor cells and transition of bone marrow-derived neuronal cells. Circulation. 2006;113:701-10 pubmed
    ..Because G-CSF and SCF are available for clinical use, these findings suggest a new therapeutic strategy for stroke. ..
  5. Perrin C, Bayle J, Bannwarth S, Michiels J, Heudier P, Lefebvre J, et al. Expression of LSLCL, a new C-type lectin, is closely restricted, in bone marrow, to immature neutrophils. C R Acad Sci III. 2001;324:1125-32 pubmed
    ..Since LSLCL and various closely related cDNAs are expressed at definite stages of cellular maturation processes, we hypothesize that this class of proteins could play an important role in the control of cellular differentiation...
  6. Zsebo K, Wypych J, McNiece I, Lu H, Smith K, Karkare S, et al. Identification, purification, and biological characterization of hematopoietic stem cell factor from buffalo rat liver--conditioned medium. Cell. 1990;63:195-201 pubmed
    ..It is also a growth factor for mast cells. In two companion papers, we present the sequences of partial SCF cDNAs, identify SCF as a c-kit ligand, and map the SCF gene to the Sl locus of the mouse. ..
  7. Williams D, Eisenman J, Baird A, Rauch C, Van Ness K, March C, et al. Identification of a ligand for the c-kit proto-oncogene. Cell. 1990;63:167-74 pubmed
    ..This establishes MGF as a ligand for the c-kit protein. ..
  8. Broudy V, Kovach N, Bennett L, Lin N, Jacobsen F, Kidd P. Human umbilical vein endothelial cells display high-affinity c-kit receptors and produce a soluble form of the c-kit receptor. Blood. 1994;83:2145-52 pubmed
    ..The production of soluble c-kit receptors by normal human endothelial cells may serve to regulate the bioactivity of SCF within the bone marrow microenvironment. ..
  9. Nowrousian M, Waschke S, Bojko P, Welt A, Schuett P, Ebeling P, et al. Impact of chemotherapy regimen and hematopoietic growth factor on mobilization and collection of peripheral blood stem cells in cancer patients. Ann Oncol. 2003;14 Suppl 1:i29-36 pubmed

More Information


  1. Calhoun D. Enteral administration of hematopoietic growth factors in the neonatal intensive care unit. Acta Paediatr Suppl. 2002;91:43-53 pubmed
    ..This review discusses cytokines with known GI trophic effects, either in vitro or in vivo, and focuses on those cytokines that have been used in the neonatal intensive care unit. ..
  2. Wolff S. Second hematopoietic stem cell transplantation for the treatment of graft failure, graft rejection or relapse after allogeneic transplantation. Bone Marrow Transplant. 2002;29:545-52 pubmed
    ..However, a lack of well-designed prospective studies has made definitive recommendations difficult although basic principles have been established. ..
  3. Wang Y, Lu C, Wei H, Wang N, Chen X, Zhang L, et al. Hepatopoietin interacts directly with COP9 signalosome and regulates AP-1 activity. FEBS Lett. 2004;572:85-91 pubmed
    ..Taken together, these results elucidate a novel relationship of intracellular growth factor, HPO with large protein complex, CSN, which suggests a possible linkage between CSN and liver regeneration. ..
  4. Sadlon T, Lewis I, D Andrea R. BMP4: its role in development of the hematopoietic system and potential as a hematopoietic growth factor. Stem Cells. 2004;22:457-74 pubmed
    ..We discuss evidence that BMP4 acts as a hematopoietic growth factor and review its potential to modulate HSC in ex vivo expansion cultures from cord blood. ..
  5. Horn P, Morris J, Bukovsky A, Andrews R, Naldini L, Kurre P, et al. Lentivirus-mediated gene transfer into hematopoietic repopulating cells in baboons. Gene Ther. 2002;9:1464-71 pubmed
    ..In conclusion, these results suggest that lentiviral vectors are able to tranduce multilineage hematopoietic stem cells, and thus, may provide an alternative vector system for clinical stem cell gene therapy applications. ..
  6. Gallagher R, Tura Ceide O, Turner M, Barclay R. Analysis of Wnt pathway genes during ex vivo expansion and neutrophil differentiation of umbilical-cord-blood-derived CD34 cells. Vox Sang. 2010;98:e290-4 pubmed publisher
  7. Liu P, Hsieh W, Huang S, Liao H, Chiang B. Hematopoietic effect of water-soluble polysaccharides from Angelica sinensis on mice with acute blood loss. Exp Hematol. 2010;38:437-45 pubmed publisher
    ..05) during ex vivo test. Results of this study demonstrated the potential of ASPS for treatment of anemia. ..
  8. Holm M, Hoyer M, Jensen I, Thomsen M, Hokland P. Dynamic cell cycle kinetics in vitro and in vivo in myelodysplastic syndromes with special reference to the influence of hematopoietic growth factors. Leuk Res. 2000;24:999-1008 pubmed
    ..6 to 3.5 days. Importantly, we demonstrated that in vivo GM-CSF administration to patients with RAEB resulted in a shortening of T(pot) within the 2 first weeks of GM-CSF treatment. ..
  9. Ribatti D, Vacca A, De Falco G, Ria R, Roncali L, Dammacco F. Role of hematopoietic growth factors in angiogenesis. Acta Haematol. 2001;106:157-61 pubmed
  10. Hassan N, Chehimi J, Ho W, Campbell D, Douglas S. Effect of hematopoietic growth factors on human blood monocytes/macrophages in in vitro culture. Clin Diagn Lab Immunol. 1994;1:620-5 pubmed
  11. Sansilvestri P, Cardoso A, Batard P, Panterne B, Hatzfeld A, Lim B, et al. Early CD34high cells can be separated into KIThigh cells in which transforming growth factor-beta (TGF-beta) downmodulates c-kit and KITlow cells in which anti-TGF-beta upmodulates c-kit. Blood. 1995;86:1729-35 pubmed
    ..Autocrine TGF-beta 1 appears to maintain these cells in a quiescent state, suppressing cell division by downmodulating the receptor of SF, a key cytokine costimulator of early progenitors. ..
  12. Worth L, Jeha S, Kleinerman E. Biologic response modifiers in pediatric cancer. Hematol Oncol Clin North Am. 2001;15:723-40, ix pubmed
    ..The challenge is to incorporate biologic response modifiers into the treatment armamentarium in ways that will maximize their tumorigenicity. ..
  13. Pan K, Zhu B, Wu Y. [The murine submandibular gland conditioned medium induce the development of CFU-GM and CFU-meg]. Hua Xi Yi Ke Da Xue Xue Bao. 2001;32:405-7, 482 pubmed
    ..Our study provide the experimental evidences for clarifying the relationship between submandibular gland and hematopoiesis. ..
  14. Knopp M, Bischoff H, Rimac A, Oberdorfer F, van Kaick G. Bone marrow uptake of fluorine-18-fluorodeoxyglucose following treatment with hematopoietic growth factors: initial evaluation. Nucl Med Biol. 1996;23:845-9 pubmed
    ..FDG uptake was a very sensitive marker of stimulated hematopoiesis, and both the extension and the intensification of uptake have to be noted during HGF therapy. ..
  15. Drize N, Ershler M, Chertkov I. Radiation-induced hemopoietic cell growth factor: detection in a culture. Bull Exp Biol Med. 2001;132:1213-5 pubmed
    ..It was found that in irradiated mice this activity is produced by bones. ..
  16. Bruno L, Hoffmann R, McBlane F, Brown J, Gupta R, Joshi C, et al. Molecular signatures of self-renewal, differentiation, and lineage choice in multipotential hemopoietic progenitor cells in vitro. Mol Cell Biol. 2004;24:741-56 pubmed
    ..These are likely to include genes important in self-renewal, the maintenance of multipotentiality, or the negative regulation of differentiation per se. ..
  17. Witt V, Fischmeister G, Scharner D, Printz D, Pöttschger U, Fritsch G, et al. Collection efficiencies of MNC subpopulations during autologous CD34+ peripheral blood progenitor cell (PBPC) harvests in small children and adolescents. J Clin Apher. 2001;16:161-8 pubmed
    ..We present regression equations that predict the cell yield of various MNC subpopulations in apheresis products. ..
  18. Avalos B. Molecular analysis of the granulocyte colony-stimulating factor receptor. Blood. 1996;88:761-77 pubmed
  19. Ishii T, Zhao Y, Shi J, Sozer S, Hoffman R, Xu M. T cells from patients with polycythemia vera elaborate growth factors which contribute to endogenous erythroid and megakaryocyte colony formation. Leukemia. 2007;21:2433-41 pubmed
  20. Uchida N, Otsuka T, Shigematsu H, Maeda M, Sugio Y, Itoh Y, et al. Differential gene expression of human telomerase-associated protein hTERT and TEP1 in human hematopoietic cells. Leuk Res. 1999;23:1127-32 pubmed
  21. Tsopra O, Ziros P, Lagadinou E, Symeonidis A, Kouraklis Symeonidis A, Thanopoulou E, et al. Disease-related anemia in chronic lymphocytic leukemia is not due to intrinsic defects of erythroid precursors: a possible pathogenetic role for tumor necrosis factor-alpha. Acta Haematol. 2009;121:187-95 pubmed publisher
    ..Disease-related anemia in chronic lymphocytic leukemia (CLL) occurs when the obvious causes are excluded while its pathogenesis is still obscure. We investigated its underlying mechanisms in 56 untreated patients with CLL...
  22. Jing Q, Cai H, Du Z, Ye Z, Tan W. Effects of agitation speed on the ex vivo expansion of cord blood hematopoietic stem/progenitor cells in stirred suspension culture. Artif Cells Nanomed Biotechnol. 2013;41:98-102 pubmed publisher
    ..These data indicated that HSPCs should be cultured at relatively low agitation speed and for a short-term period when cultured in stirred suspension system. ..
  23. Xu X, Huang H, Cai M, Qian Y, Han Y, Xiao L, et al. Serum hematopoietic growth factors as diagnostic and prognostic markers of acute renal allograft rejection: a potential role for serum stem cell factor. Cytokine. 2011;56:779-85 pubmed publisher
    ..A direct correlation was observed between SCF levels and the occurrence of acute renal allograft rejection which may represent an effective diagnostic and predictive biomarker for acute cellular renal allograft rejection. ..
  24. McNiece I, Briddell R. Stem cell factor. J Leukoc Biol. 1995;58:14-22 pubmed
    ..Other potential clinical uses include ex vivo expansion protocols and in vitro culture for gene therapy. ..
  25. Morrison Graham K, Takahashi Y. Steel factor and c-kit receptor: from mutants to a growth factor system. Bioessays. 1993;15:77-83 pubmed
  26. Ezoe K, Holmes S, Ho L, Bennett C, Bolognia J, Brueton L, et al. Novel mutations and deletions of the KIT (steel factor receptor) gene in human piebaldism. Am J Hum Genet. 1995;56:58-66 pubmed
    ..Thus, most patients with typical piebaldism appear to have abnormalities of the KIT gene. ..
  27. Sperr W, Czerwenka K, Mundigler G, Muller M, Semper H, Klappacher G, et al. Specific activation of human mast cells by the ligand for c-kit: comparison between lung, uterus and heart mast cells. Int Arch Allergy Immunol. 1993;102:170-5 pubmed
    ..Furthermore, MCs could be desensitized specifically by pre-incubation of MCs with rhSCF in Ca-free medium. Together, these data suggest that SCF triggers mediator secretion from MCs in various organs via binding to the c-kit receptor. ..
  28. Haines I, Olver I. Are guidelines on use of colony-stimulating factors in solid cancers flawed?. Intern Med J. 2009;39:259-62 pubmed publisher
    ..We would urge that we continue to be rigorous in our oversight of international research agendas and international clinical guidelines in the future. ..
  29. Testa U. [Physiopathology and possible clinical use of hematopoietic stem cells. Recent advances]. Recenti Prog Med. 2009;100:144-55 pubmed
  30. Patole S, Vijayakumar P, Jog S. Perinatal immunomodulation. J Matern Fetal Neonatal Med. 2002;11:290-301 pubmed
    ..The current immunomodulators/immunotherapeutic agents with established/potential clinical applications in the perinatal period are reviewed. ..
  31. Keller G, Wall C, Fong A, Hawley T, Hawley R. Overexpression of HOX11 leads to the immortalization of embryonic precursors with both primitive and definitive hematopoietic potential. Blood. 1998;92:877-87 pubmed
    ..In addition, they suggest that LIF could play a role in the regulation of primitive erythropoiesis. ..
  32. Piacibello W, Sanavio F, Severino A, Garetto L, Dane A, Gammaitoni L, et al. Ex vivo expansion of cord blood progenitors. Vox Sang. 1998;74 Suppl 2:457-62 pubmed
  33. Josefsen D, Myklebust J, Lynch D, Stokke T, Blomhoff H, Smeland E. Fas ligand promotes cell survival of immature human bone marrow CD34+CD38- hematopoietic progenitor cells by suppressing apoptosis. Exp Hematol. 1999;27:1451-9 pubmed
    ..In agreement with previous reports, FasL alone slightly increased cell death of more mature CD34(-)CD38+ cells, indicating an interesting shift in the responsiveness to FasL during early hematopoiesis. ..
  34. Kolb G. [Myelopoiesis and bone marrow function in elderly tumor patients]. Z Gerontol Geriatr. 2012;45:197-200 pubmed publisher
    ..However, prognostic tests to predict the individual risk of hematotoxicity and septicemia are lacking. ..
  35. Seshi B, Kumar S, Sellers D. Human bone marrow stromal cell: coexpression of markers specific for multiple mesenchymal cell lineages. Blood Cells Mol Dis. 2000;26:234-46 pubmed
    ..Also, this new understanding of bone marrow stromal cells as "one cell with many different faces" promises to advance our knowledge of regulatory cellular interactions within bone marrow. ..
  36. Gronda M, Bianchi de Di Risio C. [Hematopoiesis regulation]. Medicina (B Aires). 1993;53:167-75 pubmed
    ..However, the mechanisms underlying growth/inhibitory factor production and progenitor cell proliferation remain poorly understood. ..
  37. Wu H, Klingmuller U, Besmer P, Lodish H. Interaction of the erythropoietin and stem-cell-factor receptors. Nature. 1995;377:242-6 pubmed
    ..Our results indicate that KIT may activate the EPO receptor by tyrosine phosphorylation to induce further proliferation and maturation of CFU-Es. ..
  38. Chatta G, Dale D. Aging and haemopoiesis. Implications for treatment with haemopoietic growth factors. Drugs Aging. 1996;9:37-47 pubmed
    ..However, we still need to better elucidate age-related changes in the early stages of haemopoiesis. The question of haemopoietic exhaustion, particularly under prolonged growth factor stimulation, is real and still unanswered. ..
  39. Thevenot T, Cadranel J, Di Martino V, Pariente A, Causse X, Renou C, et al. A national French survey on the use of growth factors as adjuvant treatment of chronic hepatitis C. Hepatology. 2007;45:377-83 pubmed
    ..The suitable role of EPO and G-CSF as complements to HCV therapy urgently needs to be clarified. ..
  40. Hidalgo A, Sanz Rodriguez F, Rodríguez Fernandez J, Albella B, Blaya C, Wright N, et al. Chemokine stromal cell-derived factor-1alpha modulates VLA-4 integrin-dependent adhesion to fibronectin and VCAM-1 on bone marrow hematopoietic progenitor cells. Exp Hematol. 2001;29:345-55 pubmed
    ..Modulation of VLA-4-mediated CD34(hi) BM cell adhesion by SDF-1alpha could play a key role in their migration within and to the BM and therefore influence their proliferation and differentiation. ..
  41. Bay J, Peffault De Latour R, Tournilhac O, Choufi B, Chassagne J. [Hematopoietic growth factors and autologous or allogeneic stem cell transplantation]. Bull Cancer. 2006;93:473-82 pubmed
    ..The new long acting growth factors such as pegfilgrastim are still under evaluation and their use in mobilization seems promising. ..
  42. Kobune M, Kato J, Chiba H, Kawano Y, Tanaka M, Takimoto R, et al. Telomerized human bone marrow-derived cell clones maintain the phenotype of hematopoietic-supporting osteoblastic and myofibroblastic stromal cells after long-term culture. Exp Hematol. 2005;33:1544-53 pubmed
    ..HTS cells may be useful for analyzing the molecular mechanism of hematopoietic support of human stromal cells. ..
  43. Haas R, Bruns I, Kobbe G, Fenk R. High-dose therapy and autologous peripheral blood stem cell transplantation in patients with multiple myeloma. Recent Results Cancer Res. 2011;183:207-38 pubmed publisher
    ..In this chapter we will review the progress, which has been made in order to enhance the mobilisation of autologous stem cells and increase the effectiveness of this treatment. ..
  44. Afenya E. Recovery of normal hemopoiesis in disseminated cancer therapy--a model. Math Biosci. 2001;172:15-32 pubmed
  45. Alexander W, Roberts A, Nicola N, Li R, Metcalf D. Deficiencies in progenitor cells of multiple hematopoietic lineages and defective megakaryocytopoiesis in mice lacking the thrombopoietic receptor c-Mpl. Blood. 1996;87:2162-70 pubmed
    ..Moreover, our results also imply an important role for TPO and c-Mpl in the production of primitive pluripotent progenitor cells as well as progenitor cells committed to nonmegakaryocytic lineages. ..
  46. Testa U, Pelosi E, Gabbianelli M, Fossati C, Campisi S, Isacchi G, et al. Cascade transactivation of growth factor receptors in early human hematopoiesis. Blood. 1993;81:1442-56 pubmed
  47. Chiarugi V, Dello Sbarba P, Magnelli L, Chiarugi P, Pacini S, Ruggiero M. Cytokine receptor signal transduction mechanisms in immuno-hematopoietic cells. Tumori. 1993;79:92-9 pubmed
    ..Three of five classes of receptors show the involvement of tyrosine kinase activity as the key step in signal transduction. The importance of tyrosine phosphorylation in cellular response to cytokines is pointed out. ..
  48. Agis H, Willheim M, Sperr W, Wilfing A, Kromer E, Kabrna E, et al. Monocytes do not make mast cells when cultured in the presence of SCF. Characterization of the circulating mast cell progenitor as a c-kit+, CD34+, Ly-, CD14-, CD17-, colony-forming cell. J Immunol. 1993;151:4221-7 pubmed
    ..This is the first definitive demonstration that mast cells are replenished directly from early hemopoietic progenitors and thus form a unique cell lineage within the hemopoietic system. ..
  49. Ramirez Bergeron D, Runge A, Adelman D, Gohil M, Simon M. HIF-dependent hematopoietic factors regulate the development of the embryonic vasculature. Dev Cell. 2006;11:81-92 pubmed
    ..These results suggest that HIF coordinates early endothelial cell emergence and vessel development by promoting hematopoietic cell survival and paracrine growth factor production. ..
  50. Mughal T. Current and future use of hematopoietic growth factors in cancer medicine. Hematol Oncol. 2004;22:121-34 pubmed
    ..Thrombopoietin is currently in clinical trials to assess its potential role in the treatment of thrombocytopenia in patients with cancer. ..
  51. Padilla G, Ropka M. Quality of life and chemotherapy-induced neutropenia. Cancer Nurs. 2005;28:167-71 pubmed
    ..To assess the effect of such interventions, neutropenia-specific QOL instruments, such as the Functional Assessment of Cancer Therapy-Neutropenia (FACT-N), may be valuable tools. ..
  52. Parravicini E, van de Ven C, Anderson L, Cairo M. Myeloid hematopoietic growth factors and their role in prevention and/or treatment of neonatal sepsis. Transfus Med Rev. 2002;16:11-24 pubmed
  53. Kwiatkowski B, Bastian L, Bauer T, Tsai S, Zielinska Kwiatkowska A, Hickstein D. The ets family member Tel binds to the Fli-1 oncoprotein and inhibits its transcriptional activity. J Biol Chem. 1998;273:17525-30 pubmed