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The role of hypoxia in the maintenance of hematopoietic stem cells
MG Cipolleschi, P Dello Sbarba and M Olivotto
Istituto di Patologia Generale, Universita di Firenze, Florence, Italy.
Bone marrow cell liquid cultures were incubated at various oxygen
concentrations ranging from 0% to 18% (air). The total number of cells in
culture (CT) at the end of a 6-day incubation was found to be directly
proportional to the oxygen concentration. As compared with air- incubated
controls, cells recovered from severely hypoxic (1% oxygen) day-5 liquid
cultures showed (1) the same day-7 colony-formation efficiency in semisolid
culture (neutrophilic/monocytic colonies) or in spleen; (2) a higher day-14
spleen colony-formation efficiency; (3) an enhanced radio-protection
ability; and (4) an increased marrow repopulation ability, as measured by
determining either total cell number in recipient marrow MRAcell, or the
capacity of the latter of generating day-7 neutrophilic/monocytic colonies
in secondary in vitro assays (MRACFU-NM). Taking into account CT, the
absolute numbers of progenitors in culture were also computed. The results
showed that, with respect to time 0, incubation in air produced an increase
in the number of day-7 CFUs and a decrease in the number of the other
progenitors, whereas in hypoxic cultures all types of progenitors
decreased. However, as compared with air-incubated controls, all
progenitors, except cells sustaining MRACFU-NM, were reduced in hypoxic
cultures. The degree of reduction paralleled the position of the progenitor
in the hematopoietic hierarchy, being maximum for day-7 CFUs and null for
cells sustaining MRACFU-NM, which, in fact, were better preserved in
hypoxic cultures.
Volume 82,
Issue 7,
pp. 2031-2037,
10/01/1993
Copyright © 1993 by The American Society of Hematology
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