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Hematopoietic supportive functions of mouse bone marrow and fetal liver
microenvironment: dissection of granulocyte, B-lymphocyte, and
hematopoietic progenitor support at the stroma cell clone level
C Friedrich, E Zausch, SP Sugrue and JC Gutierrez-Ramos
Center for Blood Research, Inc and Departments of Genetics and Anatomy and
Cellular Biology, Harvard Medical School, Boston, MA 02115, USA.
We dissected the functions of the microenvironment of bone marrow (BM) and
fetal liver (FL) at the cellular level by cloning individual stromal calls
and characterizing their phenotypical and functional features. Stromal cell
clones derived from FL are large in size (mean forward light scatter
intensity [mFSC] of 450), express the surface antigen Thy-1 but not Sca-1
and 6 out of 6 are able to differentiate into fat accumulating adipocytes.
BM derived stromal cell clones are either small (mFSC of 250) or large
(mFSC of 450), express Sca-1 but not Thy-1 and only 2 out of 7
differentiate towards adipocytes. Heterogeneity in terms of vascular
adhesion molecule-1, intracellular adhesion molecule-1 and heat stable
antigen expression was found among the different cell clones. Functional
assays using long- and short-term cocultures of stromal and hematopoietic
calls revealed: (1) the capacity of 8 out of 12 stromal cell clones to
support the expansion of primitive hematopoietic progenitors (colony
forming unit spleen day 12) more than 10 weeks. Fat accumulation but not
expression of stem cell factor by stromal cells did correlate with this
supportive function. (2) Better support of granulocyte maturation and
proliferation by BM- compared to FL-derived stromal cell clones. However,
stromal cell clones from both organs expressed macrophage-colony
stimulating factor. (3) The ability of 4 out of 12 stromal cell clones
(derived from both, FL and BM) to support the expansion of Interleukin-7
dependent pre-B cells from the BM. Pre-B cell growth stimulating factor was
not restricted to supporters. (4) Mutual exclusiveness of myeloid and
lymphoid support in that a given stromal cell clone supported either pre
B-cell or granulocyte expansion. Experiments comparing the support of BM-
and FL-derived hematopoietic progenitors showed identical responses of late
(B220+/c-kit-) but strikingly different responses of early (B220+/c-kit+)
pre-B cells, revealing different proliferation requirements for FL- versus
BM- derived early pre-B cells in vitro.
Volume 87,
Issue 11,
pp. 4596-4606,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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