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Blood, Vol. 92 No. 10 (November 15), 1998:
pp. 3658-3668
Growth and Differentiation of Human Stem Cell
Factor/Erythropoietin-Dependent Erythroid Progenitor Cells In Vitro
Birgit Panzenböck,
Petr Bartunek,
Markus Y. Mapara, and
Martin Zenke
From the Max-Delbrück-Centre for Molecular Medicine, MDC,
Berlin, Germany; and the Humboldt University Berlin, Virchow Klinikum,
Robert-Rössle-Klinik, Berlin, Germany.
Stem cell factor (SCF) and erythropoietin (Epo) effectively support
erythroid cell development in vivo and in vitro. We have studied here
an SCF/Epo-dependent erythroid progenitor cell from cord blood that can
be efficiently amplified in liquid culture to large cell numbers in the
presence of SCF, Epo, insulin-like growth factor-1
(IGF-1), dexamethasone, and estrogen. Additionally, by
changing the culture conditions and by administration of Epo plus
insulin, such progenitor cells effectively undergo terminal differentiation in culture and thereby faithfully recapitulate erythroid cell differentiation in vitro. This SCF/Epo-dependent erythroid progenitor is also present in CD34+ peripheral
blood stem cells and human bone marrow and can be isolated, amplified,
and differentiated in vitro under the same conditions. Thus, highly
homogenous populations of SCF/Epo-dependent erythroid progenitors can
be obtained in large cell numbers that are most suitable for further
biochemical and molecular studies. We demonstrate that such cells
express the recently identified adapter protein p62dok that
is involved in signaling downstream of the c-kit/SCF receptor. Additionally, cells express the cyclin-dependent kinase (CDK) inhibitors p21cip1 and p27kip1 that are highly
induced when cells differentiate. Thus, the in vitro system described
allows the study of molecules and signaling pathways involved in
proliferation or differentiation of human erythroid cells.
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