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Demonstration of stem cell inhibition and myeloprotective effects of
SCI/rhMIP1 alpha in vivo
DJ Dunlop, EG Wright, S Lorimore, GJ Graham, T Holyoake, DJ Kerr, SD Wolpe and IB Pragnell
CRC Beatson Laboratories, Bearsden, Glasgow.
The proliferative status of the stem cell compartment is thought to be
controlled by both positive and negative regulators of proliferation. These
regulators have obvious clinical potential in manipulating the integrity
and proliferative status of the stem cell in vivo during patient treatment
for neoplastic disease. We have tested the ability of the human recombinant
homologue of murine macrophage inflammatory protein-1 alpha (rhMIP1 alpha)
to suppress the proliferation of primitive murine progenitors in vitro and
in vivo. This recombinant protein (stem cell inhibitor, similar to the
human homologue of MIP 1 alpha, LD78) is active in a dose-dependent manner
in vitro on CFU-S measured at day 12 and to a slightly lesser extent on the
more mature CFU-S that are measured at day 8. SCI/rhMIP1 alpha is also
active in vivo in two separate models of bone marrow regeneration in which
the high proliferative status of the CFU-S compartment is reduced to the
quiescent state with a single inoculation of SCI/rhMIP1 alpha. The
inhibitory activity of the recombinant protein was then tested in a
relevant therapeutic model in which the observed protection of part of the
stem cell compartment is reflected by a significant improvement in the
kinetics of neutrophil recovery. These results establish the feasibility of
testing SCI/rhMIP1 alpha in a range of chemotherapy regimes as a
preliminary to clinical trials to attempt to protect the stem cell
compartment during treatment for neoplastic disease.
Volume 79,
Issue 9,
pp. 2221-2225,
05/01/1992
Copyright © 1992 by The American Society of Hematology
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