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Characterization of primitive hematopoietic cells in normal human
peripheral blood
C Udomsakdi, PM Lansdorp, DE Hogge, DS Reid, AC Eaves and CJ Eaves
Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver, Canada.
The total number of clonogenic cells present in 5-week-old long-term
cultures (LTC) initiated by seeding normal human marrow cells on competent
adherent cell feeder layers allows for the quantitation of a more primitive
hematopoietic input precursor cell type referred to as an LTC-initiating
cell (LTC-IC). Previous studies have suggested that LTC-IC also circulate
because production of clonogenic cells continues for many weeks when cells
from the light-density (< 1.077 g/mL), T-cell- depleted fraction of
normal blood are maintained on irradiated, marrow- derived feeder layers in
LTC medium. We now show that the number of clonogenic cells present in such
reconstructed LTC after 5 weeks is linearly related to the input number of
peripheral blood (PB) cells over a wide range of cell concentrations,
thereby permitting the quantitation of circulating LTC-IC by limiting
dilution analysis. Using this approach, we have found the concentration of
LTC-IC in the circulation of normal adults to be 2.9 +/- 0.5/mL. This is
approximately 75-fold lower than the concentration of circulating
clonogenic cells (ie, burst-forming units-erythroid plus colony-forming
units [CFU] granulocyte-macrophage plus CFU-granulocyte, erythroid,
monocyte, megakaryocyte) and represents a frequency of LTC-IC relative to
all nucleated cells that is approximately 100-fold lower than that measured
in normal marrow aspirate samples. Characterization studies showed most
circulating LTC-IC to be small (low forward light scatter and side
scatter), CD34+, Rh-123dull, HLA-DR-, and 4-
hydroperoxycyclophosphamide-resistant cells, with differentiative and
proliferative potentialities indistinguishable from LTC-IC in normal
marrow. Isolation of the light-density, T-cell-depleted, CD34+, and either
HLA-DR(low) or Rh-123(dull) fraction of normal blood yielded a highly
enriched population of cells that were 0.5% to 1% LTC-IC (approximately
1,500-fold enriched beyond the light-density, T-cell- depletion step), a
purity comparable to the most enriched populations of human marrow LTC-IC
reported to date. However, purification of PB LTC-IC on the basis of these
properties did not allow them to be physically separated from a substantial
proportion (> 30%) of the clonogenic cells in the same samples, in
contrast to previous findings for LTC-IC and clonogenic cells in marrow.
These studies show the presence in the blood of normal adults of a
relatively small but readily detectable population of functionally defined,
primitive hematopoietic cells that share properties with marrow LTC-IC, a
cell type thought to have in vivo reconstituting potential.(ABSTRACT
TRUNCATED AT 400 WORDS)
Volume 80,
Issue 10,
pp. 2513-2521,
11/15/1992
Copyright © 1992 by The American Society of Hematology
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