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Functional heterogeneity of the hematopoietic microenvironment: rare
stromal elements maintain long-term repopulating stem cells
J Wineman, K Moore, I Lemischka and C Muller-Sieburg
Medical Biology Institute, La Jolla, CA 92037, USA.
It has been hypothesized that distinct stromal cells from niches within the
microenvironment that selectively regulate stem cell functions. To test
this hypothesis, we derived a panel of matched stromal cell lines from
murine fetal liver. The lines were immortalized with a retroviral vector
encoding a temperature sensitive SV40 T antigen, to provide a snapshot of
potential heterogeneity of the in vivo stroma compartment. All the stromal
cell lines tested, supported the proliferation and differentiation of
myeloid cells in Dexter type bone marrow cultures. Furthermore, RT-PCR
analysis indicates that these lines are similar with respect to the
production of an array of cytokines. However, the stromal cell lines
differed markedly in their ability to maintain in vitro stem cells with in
vivo repopulating capacity. Stem cell levels were measured in the
competitive repopulation assay, following 3 weeks of coculture on
individual stromal cell lines. Three classes of stromal cell lines were
identified: (1) lines that did not support stem cells, (2) lines that
sustained low levels of stem cells that often showed limited persistence in
vivo, and (3) an infrequent line (1 out of 16 lines tested) that maintained
high levels of primitive, long-term repopulating stem cells. This suggests
that stromal cells that can support primitive stem cells are rare in the
hematopoietic microenvironment. Taken together, these data substantiate the
hypothesis that distinct stromal cells interact selectively with stem
cells.
Volume 87,
Issue 10,
pp. 4082-4090,
05/15/1996
Copyright © 1996 by The American Society of Hematology

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