Oxygen tension influences the differentiation, maturation and apoptosis of human megakaryocytes

Sigma S. Mostafa, William M Miller, E. Terry Papoutsakis

Research output: Contribution to journalArticle

79 Scopus citations

Abstract

Megakaryocytes (Mks) mature adjacent to bone marrow (BM) sinus walls and subsequently release platelets within the sinusoidal space or in lung capillaries. As the sites for platelet release have higher levels of oxygen tension (pO2) than the core of the BM where stem and progenitor cells reside, we investigated whether pO2 influences Mk maturation. Mks were generated from CD34+ cells (from mobilized peripheral blood from cancer patients) under 5% and 20% O2. At day 15. CD41+ Mk expansion in 20% and 5% O2 cultures was 85-fold and 31-fold respectively. Twenty percent O2 cultures also had higher levels of high ploidy (≥ 8N. eightfold higher) and proplatelet-forming (fivefold higher) Mks. At day 21. 20% O2 cultures had a fivefold higher number of apoptotic Mks. In contrast. 5% O2 promoted Mk colony-forming unit (CFU-Mk) generation and maintenance. Similar results were observed in cultures initiated with CD41+ Mks, indicating that pO2 directly affects Mks. The change from 20% to 5% O2 on day 5 and day 7 delayed both maturation and apoptosis, suggesting that these two processes are closely linked. These results were confirmed in CD34+ cultures from normal BM samples. These data may provide insights into in vivo Mk maturation, such as an explanation for hypoxia-induced thrombocytopenia in animals.

Original languageEnglish (US)
Pages (from-to)879-889
Number of pages11
JournalBritish Journal of Haematology
Volume111
Issue number3
DOIs
StatePublished - Dec 1 2000

Keywords

  • Apoptosis
  • Differentiation
  • Maturation
  • Megakaryocytes
  • Oxygen tension

ASJC Scopus subject areas

  • Hematology

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