DOI: 10.1182/blood.v90.6.2234. In Vitro Senescence and Apoptotic Cell Death of Human Megakaryocytes

In Vitro Senescence and Apoptotic Cell Death of Human Megakaryocytes

10.1182/blood.v90.6.2234

Crossref journal-article

American Society of Hematology

Blood (234)

Abstract

AbstractTo investigate the fate of human megakaryocytes, CD34+ hematopoietic progenitor cells were purified from the peripheral blood or bone marrow of healthy donors and seeded in serum-free chemically defined suspension cultures. In the presence of thrombopoietin (TPO; 100 ng/mL), CD34-derived cells showed an eightfold numerical expansion and a progressive maturation along the megakaryocytic lineage. Megakaryocyte maturation was characterized ultrastructurally by the presence of a demarcation membrane system and phenotypically by a high surface expression of αIIbβ3 integrin. The number of mature megakaryocytes peaked at days 12 to 15 of culture. On the other hand, the number of platelets released in the culture supernatant by CD34-derived megakaryocytes peaked at days 18 to 21, when a high percentage of megakaryocytes showed the characteristic features of apoptosis, as evaluated by electron microscopy, terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick end-labeling technique (TUNEL) and uptake of propidium iodide. In other experiments, primary αIIbβ3+ megakaryocytic cells were directly purified from the bone marrow aspirates of normal donors and seeded in serum-free suspension cultures. In the absence of cytokines, αIIbβ3+ megakaryocytes progressively underwent apoptotic cell death. The addition of TPO but not interleukin-3 or erythropoietin showed some protection of αIIbβ3+ cells from apoptosis at early culture times (days 2 to 4), but it did not show any significant effect at later time points. These findings suggest that the terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis, which can be modulated only to a certain extent by TPO.

Bibliography

Zauli, G., Vitale, M., Falcieri, E., Gibellini, D., Bassini, A., Celeghini, C., Columbaro, M., & Capitani, S. (1997). In Vitro Senescence and Apoptotic Cell Death of Human Megakaryocytes. Blood, 90(6), 2234â2243.

Authors 8

Giorgio Zauli (first)
Marco Vitale (additional)
Elisabetta Falcieri (additional)
Davide Gibellini (additional)
Alessandra Bassini (additional)
Claudio Celeghini (additional)
Marta Columbaro (additional)
Silvano Capitani (additional)

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Dates

Type	When
Created	5 years, 10 months ago (Oct. 13, 2019, 11:35 p.m.)
Deposited	1 year, 11 months ago (Sept. 21, 2023, 12:05 p.m.)
Indexed	2 months, 2 weeks ago (June 16, 2025, 4:46 p.m.)
Issued	27 years, 11 months ago (Sept. 15, 1997)
Published	27 years, 11 months ago (Sept. 15, 1997)
Published Print	27 years, 11 months ago (Sept. 15, 1997)

Funders 0

None

BibTeX

@article{Zauli_1997, title={In Vitro Senescence and Apoptotic Cell Death of Human Megakaryocytes}, volume={90}, ISSN={0006-4971}, url={http://dx.doi.org/10.1182/blood.v90.6.2234}, DOI={10.1182/blood.v90.6.2234}, number={6}, journal={Blood}, publisher={American Society of Hematology}, author={Zauli, Giorgio and Vitale, Marco and Falcieri, Elisabetta and Gibellini, Davide and Bassini, Alessandra and Celeghini, Claudio and Columbaro, Marta and Capitani, Silvano}, year={1997}, month=sep, pages={2234–2243} }

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  "abstract": "<jats:title>Abstract</jats:title><jats:p>To investigate the fate of human megakaryocytes, CD34+ hematopoietic progenitor cells were purified from the peripheral blood or bone marrow of healthy donors and seeded in serum-free chemically defined suspension cultures. In the presence of thrombopoietin (TPO; 100 ng/mL), CD34-derived cells showed an eightfold numerical expansion and a progressive maturation along the megakaryocytic lineage. Megakaryocyte maturation was characterized ultrastructurally by the presence of a demarcation membrane system and phenotypically by a high surface expression of \u03b1IIb\u03b23 integrin. The number of mature megakaryocytes peaked at days 12 to 15 of culture. On the other hand, the number of platelets released in the culture supernatant by CD34-derived megakaryocytes peaked at days 18 to 21, when a high percentage of megakaryocytes showed the characteristic features of apoptosis, as evaluated by electron microscopy, terminal deoxynucleotidyl transferase (TdT)-mediated d-UTP-biotin nick end-labeling technique (TUNEL) and uptake of propidium iodide. In other experiments, primary \u03b1IIb\u03b23+ megakaryocytic cells were directly purified from the bone marrow aspirates of normal donors and seeded in serum-free suspension cultures. In the absence of cytokines, \u03b1IIb\u03b23+ megakaryocytes progressively underwent apoptotic cell death. The addition of TPO but not interleukin-3 or erythropoietin showed some protection of \u03b1IIb\u03b23+ cells from apoptosis at early culture times (days 2 to 4), but it did not show any significant effect at later time points. These findings suggest that the terminal phase of the megakaryocyte life span is characterized by the onset of apoptosis, which can be modulated only to a certain extent by TPO.</jats:p>",
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