Science in China Series C: Life Sciences

, Volume 42, Issue 6, pp 591–598 | Cite as

Study of thrombopoietin for gene therapy of thrombocytopenia

  • Song Chong
  • Daru Lu
  • Changben Li
  • Xinfang Qiu
  • Jinglun Xue


Thrombopoietin (TPO) is likely to he a potent, specific and reliable medication in the treatment of thrombocytopenia. A TPO-highly-expressed plasmid pcDNA3-TPO was constructed and a primary study was made on the expression of TPO cDNAin vitro and gene transfer study for thrombocytopeniain vivo. rhTPO showed complete and stable bioactivity by a series of indicators. High expression of TPO was detected in plasma from healthy mice or thrombocytopenia mice model receiving direct intramuscular injection of pcDNA3-TPO. And the platelet level of healthy mice peaked to 1.9-fold of baseline. Mice with CTX-induced thrombocytopenia achieved profound nadirs, acceleration of recovery, even 1.8–2.0-fold supranormal levels of peripheral platelet counts. The results offered experimental support for clinical application of gene therapy for thrombocytopenia via direct intramuscular injection of TPO cDNA.


thrombopoietin (TPO) gene transfer thrombocytopenia intramuscular injection 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Kaushansky, K., Thrombopoietin: More than a lineage-specific megakaryoeyte growth factor,Stem Cells, 1997, 15(Suppl. 1): 97.PubMedCrossRefGoogle Scholar
  2. 2.
    Daw, N. C. et al., A single intravenous dose of murine megakaryocyte and development factor potentially stimulates platelet production, challenging the necessity for daily administration,Blood, 1998, 91(2): 466.PubMedGoogle Scholar
  3. 3.
    Cardier, J. E. et al., Thrombopoietin and its receptor c-mpl, are constitutively expressed by mouse liver endothelial cells: evi-dence of thrombopoietin as a growth factor for liver endothelial cells,Blood, 1998, 91(3): 923.PubMedGoogle Scholar
  4. 4.
    Yan, X. Q., Lacey, D., Hill, D. et al., A model of myelofibrosis and osteosclerosis in mice induced by overexpressing thrombopoietin(mpl-ligand): reversal of disease by bone marrow transplantation,Blood, 1996, 88: 402.PubMedGoogle Scholar
  5. 5.
    Amado, R. G., Symonds, G., Jamieson, B. D. et al., Effects of megakaryocyte growth and development factor on survival and retroviral transduction of T lymphoid cells,Human Gene Therapy, 1998, 9(2): 173.PubMedCrossRefGoogle Scholar
  6. 6.
    Cannizzo, S. J. et al., Augmentation of blood platelet levels by intratracheal administration of an adenovirus vector encoding human thrombopoietin cDNA,Nat. Biotechnol., 1997, 15: 570.PubMedCrossRefGoogle Scholar
  7. 7.
    Ohwada, A. S., Rafii, Moore, et al.,In vivo adenovirus vector-mediated transfer of the human thrombopoietin cDNA main-tains platelet levels during radiation-and chemotherapy-induced bone marrow suppression,Blood, 1996, 88: 778.PubMedGoogle Scholar
  8. 8.
    Folman, C. C., et al., Sensitive measurement of thrombopoetin by a monoclonal antibody based sandwich enzyme-linked im-munosorbent assay,Thromb. Haemost., 1997, 78(4): 1262.PubMedGoogle Scholar
  9. 9.
    Konishi, H., Ochiya, T., Sakamoto, H. et al., Effective prevention of thrombocytopenia using adenovirus mediated transfer of HST-1/FGF-4 gene:in vivo andin vitro studies,Leukemia, 1997, 11(Suppl. 3): 530.PubMedGoogle Scholar
  10. 10.
    Choi, E. S., Hokom, M. M., Chen, J. L. et al., The role of megakaryocyte growth and development in terminal stages of thrombopoiesis,Br. J. Haematol., 1996, 95(2): 227.PubMedCrossRefGoogle Scholar
  11. 11.
    Villeval, J. L., Karine, C. S., Tulliez, M. et al., High thrombopoietin production by hematopoietic cells induces a fatal myeloproliferative syndrom in mice,Blood, 1997, 90(11): 4369.PubMedGoogle Scholar
  12. 12.
    Frey, B. M. et al., Adenovector-mediated expression of human thrombopoietin cDNA in immune-compromised mice: insights into the pathophysiology of osteomyelofibrosis,J. Immunol., 1998, 160(2): 691.PubMedGoogle Scholar
  13. 13.
    Abina, M. A., Tulliez, M., Lacout, C. et al., Major effects of TPO delivered by a single injection of a recombinant aden-ovirus on prevention of septicemia and anemia associated with myelosuppression in mice: risk of sustained expression inducing myelofibrosis due to immunosuppression,Gene Ther., 1998, 5(4): 497.PubMedCrossRefGoogle Scholar
  14. 14.
    Amado, R. G., Symonds, G., Jamieson, B. D. et al., Effects of megakaryocyte growth and development factor on survival and retroviral transduction of T lymphoid cells,Human Gene Therapy, 1998, 9(2): 173.PubMedCrossRefGoogle Scholar
  15. 15.
    Cole, J. L. et al., Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients,Blood, 1998, 91(9): 3239.PubMedGoogle Scholar

Copyright information

© Science in China Press 1999

Authors and Affiliations

  • Song Chong
    • 1
  • Daru Lu
    • 1
  • Changben Li
    • 1
  • Xinfang Qiu
    • 1
  • Jinglun Xue
    • 1
  1. 1.Institute of GeneticsFudan UniversityShanghaiChina

Personalised recommendations