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In Vitro Behavior of Hematopoietic Progenitor Cells Under the
Influence of Chemoattractants: Stromal Cell-Derived Factor-1,
Steel Factor, and the Bone Marrow Environment
Chang H. Kim and
Hal E. Broxmeyer
From the Departments of Microbiology/Immunology, Medicine and the
Walther Oncology Center, Indiana University School of Medicine,
Indianapolis; and the Walther Cancer Institute, Indianapolis, IN.
How multiple chemoattractants cooperate in directing the migration
of hematopoietic progenitor cells (HPC) for homing and peripheral blood
mobilization has not yet been established. We report here the behavior
of HPC under the influence of two different chemoattractants, stromal
cell-derived factor (SDF)-1 and steel factor (SLF), and the chemotactic
nature of the bone marrow (BM) environment using a two-chamber in vitro
migration system. Various formulae were adopted to quantitate these
effects. Based on these quantitations, SDF-1 showed only chemotactic
activity, while SLF showed both chemotactic and chemokinetic activities
on factor-dependent MO7e cells. SLF, like SDF-1, attracted human HPC
from a population of CD34+ cells and induced actin
polymerization in MO7e cells. SLF and SDF-1 cooperated in attracting
MO7e cells, as well as cord blood (CB) and BM CD34+
cells. A negative concentration gradient of SLF and SDF-1, formed by
the presence of chemoattractants in the upper chamber, showed potent
inhibitory effects on MO7e cell migration induced by either of these
chemoattractants in the lower chamber, and SDF-1 and SLF were
synergistic in mobilizing cells to the lower chamber from this negative
chemoattractant gradient. Plasma obtained from BM aspirates, but not CB
or peripheral blood, showed strong chemotactic effects on BM and CB
CD34+ cells, and an inhibitory effect in a negative
gradient on SDF-1-dependent CD34+ cell migration. These
in vitro migration experiments suggest that chemoattractants such as
SDF-1 and SLF with other unidentified BM chemoattractants may be
involved cooperatively in the migration of HPC to the BM and in
preventing spontaneous mobilization of HPC out of the BM.
Blood, Vol. 91 No. 1 (January 1), 1998:
pp. 100-110
© 1998 by The American Society of Hematology.
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