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Maintenance of murine long-term repopulating stem cells in ex vivo culture
is affected by modulation of transforming growth factor-beta but not
macrophage inflammatory protein-1 alpha activities
T Soma, JM Yu and CE Dunbar
Hematology Branch, National Heart, Lung, and Blood Institute, National
Institute of Health, Bethesda, MD 20892, USA.
Transforming growth factor-beta (TGF-beta) and macrophage inflammatory
protein-l alpha (MIP-1 alpha) are both well-described inhibitors of
committed and multipotential hematopoietic progenitors. The effect of these
cytokines; on true stem cell activity in ex vivo culture systems as assayed
by murine long-term repopulating activity (LTRA) has not been examined. We
studied the stem cell effects of the addition of these cytokines to ex vivo
cultures containing interleukin-3 (IL-3), IL- 6, and stem cell factor
(SCF), using the murine competitive repopulation assay. We also tested the
impact of adding an anti-TGF- beta neutralizing antibody, to ask whether
abrogation of autocrine/paracrine TGF-beta may protect or enhance the
survival of LTRA during ex vivo culture. TGF-beta 1 had significant
suppressive effects on both short- and long-term repopulating activities,
and anti- TGF-beta antibody had enhancing effects compared with control
cultures containing IL-3, IL-6, and SCF alone. MIP-1 alpha had no
significant effects on either short- or long-term repopulating ability.
These data suggest that abrogation of TGF-beta during suspension culture
may allow enhanced survival or even expansion of primitive cells ex vivo,
with implications for many applications, including gene therapy.
Volume 87,
Issue 11,
pp. 4561-4567,
06/01/1996
Copyright © 1996 by The American Society of Hematology
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