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The "common stem cell" hypothesis reevaluated: human fetal bone marrow
contains separate populations of hematopoietic and stromal progenitors
EK Waller, J Olweus, F Lund-Johansen, S Huang, M Nguyen, GR Guo and L Terstappen
Becton Dickinson Immunocytometry Systems, San Jose, CA, USA.
There is a long-standing controversy as to whether a single bone marrow
(BM)-derived cell can differentiate along both hematopoietic and stromal
lineages. Both primitive hematopoietic and stromal progenitor cells in
human BM express the CD34 antigen but lack expression of other surface
markers, such as CD38. In this study we examined the CD34+, CD38- fraction
of human fetal BM by multiparameter fluorescence- activated cell sorting
(FACS) analysis and single-cell sorting. CD34+, C38- cells could be divided
into HLA-DR+ and HLA-DR- fractions. After single-cell sorting, 59% of the
HLA-DR+ cells formed hematopoietic colonies. In contrast, the CD34+, CD38-,
HLA-DR- cells were much more heterogeneous with respect to their light
scatter properties, expression of other hematopoietic markers (CD10, CD36,
CD43, CD49b, CD49d, CD49e, CD50, CD62E, CD90w, CD105, and CD106), and
growth properties. Single CD34+, CD38-, HLA-DR- cells sorted into
individual culture wells formed either hematopoietic or stromal colonies.
The presence or absence of CD50 (ICAM-3) expression distinguished
hematopoietic from stromal progenitors within the CD34+, CD38-, HLA-DR-
population. The CD50+ fraction had light scatter characteristics and growth
properties of hematopoietic progenitor cells. In contrast, the CD50-
fraction lacked hematopoietic progenitor activity but contained clonogenic
stromal progenitors at a mean frequency of 5%. We tested the hypothesis
that cultures derived from single cells with the CD34+, CD38- , HLA-DR-
phenotype could differentiate along both a hematopoietic and stromal
lineage. The cultures contained a variety of mesenchymal cell types and
mononuclear cells that had the morphologic appearance of histiocytes.
Immunophenotyping of cells from these cultures indicated a stromal rather
than a hematopoietic origin. In addition, the growth of the histiocytic
cells was independent of the presence or the absence of hematopoietic
growth factors. Based on sorting more than 30,000 single cells with the
CD34+, CD38-, HLA-DR- phenotype into individual culture wells, and an
analysis of 864 stromal cultures initiated by single CD34+ BM cells, this
study does not support the hypothesis of a single common progenitor for
both hematopoietic and stromal lineages within human fetal BM.
Volume 85,
Issue 9,
pp. 2422-2435,
05/01/1995
Copyright © 1995 by The American Society of Hematology
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