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Expression of CD33, CD38, and HLA-DR on CD34+ human fetal liver progenitors
with a high proliferative potential
MO Muench, J Cupp, J Polakoff and MG Roncarolo
Human Immunology Department, DNAX Research Institute, Palo Alto, CA.
High proliferative-potential colony-forming cells (HPP-CFC) have been
identified in the bone marrow of mice and adult humans, and have been
characterized as a compartment of primitive progenitors possibly including
stem cells. In this report we describe the human fetal liver (FL) as a
source of HPP-CFC. These FL HPP-CFC develop in clonal cultures in the
presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and
interleukin-3 (IL-3) within 3 to 4 weeks. The median frequency of HPP-CFC
in FL tissues between 16 and 21 weeks of gestational age was 1 in 3,000
total FL cells. After 4 weeks of growth, FL HPP-CFC grew to a median colony
size of 8.3 x 10(4) cells/colony. Using cell-sorting techniques FL HPP-CFC
were shown to be predominantly contained in the CD34+ CD33+ CD38- fraction
of FL cells. FL HPP-CFC were heterogeneous for HLA-DR expression, and no
differences in proliferative capacities were observed between HLA-DR+ and
HLA-DR- HPP- CFC. The CD34+ CD33-HLA-DR- CD38- population, previously
suggested to contain stem cells, was observed to be very rare in the FL,
representing approximately 1 in 1.7 x 10(5) light-density FL cells and
containing almost no CFC. Therefore, it is possible that stem cells are
contained in the CD33+ fraction of FL cells. Phenotypic characterization of
CD34+ CD33+ CD38- lin -LDFL cells showed that these cells are also CD13+,
predominantly Thy-1+, CD45RA-, CD45RO-, CD71-, and heterogenoeous for c-kit
expression. These data suggest that FL HPP- CFC represent a heterogeneous
compartment of primitive myeloid progenitors that may include stem cells.
Volume 83,
Issue 11,
pp. 3170-3181,
06/01/1994
Copyright © 1994 by The American Society of Hematology
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