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Development of Thrombopoietin: Its Structure and Function

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Abstract

We recently succeeded to purify thrombopoietin (TPO) from thrombocytopenic rat plasma, and to clone rat and human cDNAs, and human genome. It is now well known that TPO is a ligand of c-Mpl, a member of the hematopoietic receptor superfamily, and that TPO is a megakaryocyte lineage-dominant hematopoietic factor. Highest expression of TPO mRNA is detected in liver. We have produced two types of recombinant TPO. One is expressed in mammalian cells, and the other expressed as truncated protein in bacteria that is further modified by pegylation, termed pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF). These recombinant TPOs showed both in vitro and in vivo biological activities. Our in vitro studies have demonstrated that TPO enhances the growth of megakaryocyte progenitor cells, and the megakaryocyte maturation. In vivo study of recombinant TPO showed great increase in circulating platelet counts, and the number of megakaryocytes and its progenitor cells in the bone marrow of normal animals. Administration of recombinant TPO has effectively decreased the duration of thrombocytopenic state and accelerated platelet recovery, in myelosuppressed animal models. These findings suggest that recombinant TPO has great potential for treatment of thrombocytopenic patients.

Keywords

  • Human Thrombopoietin
  • Proplatelet Formation
  • Megakaryocyte Maturation
  • Megakaryocyte Lineage
  • Recombinant Human Thrombopoietin

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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© 1999 Kluwer Academic Publishers

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Ohgami, K. (1999). Development of Thrombopoietin: Its Structure and Function. In: Kitagawa, Y., Matsuda, T., Iijima, S. (eds) Animal Cell Technology: Basic & Applied Aspects., vol 1. Springer, Dordrecht. https://doi.org/10.1007/0-306-46865-4_20

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  • DOI: https://doi.org/10.1007/0-306-46865-4_20

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-0-7923-5451-2

  • Online ISBN: 978-0-306-46865-0

  • eBook Packages: Springer Book Archive