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In vitro megakaryocytopoietic and thrombopoietic activity of c-mpl ligand
(TPO) on purified murine hematopoietic stem cells
FC Zeigler, F de Sauvage, HR Widmer, GA Keller, C Donahue, RD Schreiber, B Malloy, P Hass, D Eaton and W Matthews
Department of Molecular Biology, Genentech, Inc, South San Francisco, CA
94080.
Recently, the ligand for c-mpl has been identified and cloned. Initial
studies of this molecule indicate that it is the platelet regulatory
factor, thrombopoietin (TPO). Previous work has indicated that c-mpl is
expressed in very immature hematopoietic precursors and thus raised the
possibility that TPO may act directly on the hematopoietic stem cell.
Therefore, in these studies, we investigate the effects of TPO on
hematopoietic stem cell populations isolated from the murine fetal liver
and bone marrow. Cocultivation of stem cells with fetal liver stroma give
rise to multilineage expansion of the stem cells but with little or no
megakaryocytopoiesis. Addition of TPO to these cocultures gives significant
megakaryocyte production. This production is enhanced in combination with
Kit ligand or interleukin-3. The addition of TPO to stem cell suspension
cultures produces a dynamic thrombopoietic system in which stem cells
undergo differentiation to produce megakaryocytes and proplatelets. These
experiments show that the megakaryocytopoietic and thrombopoietic
activities of TPO are initiated at the level of an early progenitor cell or
upon the hematopoietic stem cell.
Volume 84,
Issue 12,
pp. 4045-4052,
12/15/1994
Copyright © 1994 by The American Society of Hematology
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