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T Abe, Y Takaue, Y Kawano and Y Kuroda
Department of Pediatrics, University Hospital of Tokushima, Japan.
To investigate the effect of recombinant erythropoietin (Epo) on primitive
human hematopoietic progenitor cells, we cultured cord blood mononuclear
cells (CBMNC) and CB CD34+ cells in a Dexter-type long-term culture system
(LTC), to which various concentrations of Epo were added at day 0 or 7,
with or without direct contact with irradiated allogeneic human marrow
stromal layers. In regular stroma-contact cultures, when CBMNC were
inoculated, the addition of Epo at 1 to 10 U/mL induced a significant
increase in LTC-initiating cells (LTC-IC), particularly in the myeloid
component, compared with the control without Epo. Significantly more LTC-IC
were generated by the delayed addition of Epo on day 7 than on day 0. On
the other hand, when CD34+ cells were inoculated, physiologic
concentrations of Epo (0.1 U/mL) induced a more than twofold increase in
LTC-IC, which was attributed equally to both the myeloid and erythroid
lineages, only when added on day 0. In stroma-noncontact cultures, which
were created using a Transwell 0.4-micron microporous membrane filter,
dose-dependent suppression of the myeloid component of LTC-IC was observed
with a higher concentration of Epo (1 to 100 U/mL) when CBMNC was
inoculated. On the other hand, without Epo, fourfold more LTC-IC was
generated from CD34+ cells in stroma-noncontact than in stroma-contact
cultures, which was then significantly augmented by the addition of Epo
(0.1 or 10 U/mL) on day 0. This increase was due to both the myeloid and
erythroid lineages. A higher concentration of Epo (100 U/mL) resulted in a
decrease in LTC-IC, mainly in myeloid progeny, in all of the culture
conditions. Hence, Epo may play an important physiologic role in the
maintenance and proliferation of immature stem/progenitor cells, in close
interaction with factors from marrow stromal cells.
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| Copyright © 1996 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||