Effects of fibroblast growth factor-4 (k-FGF) on long-term cultures of
human bone marrow cells
FL Quito, J Beh, O Bashayan, C Basilico and RS Basch
Department of Pathology, Kaplan Cancer Center, New York University Medical
Center, New York, USA.
Fibroblast growth factor-4 (FGF-4), a highly mitogenic protein encoded by
the k-fgf/hst oncogene, stimulates the growth of a variety of cells of
mesenchymal and neuroectodermal origin. Addition of FGF-4 to human
long-term bone marrow cultures increased both the cell density of the
stromal layer and the number of hematopoietic colony forming cells in the
cultures in a dose-dependent manner. Hematopoiesis in the stromal layer
persisted for up to 8 months. Erythropoiesis was maintained for up to 4
weeks, but granulocytes were the predominant nonadherent cell type.
Cultures treated with FGF had increased numbers of monocytes compared with
control cultures and some CD14+, CD45+ monocytes could still be detected
after 8 months of continuous culture. The addition of the growth factor
increased the rate of growth of the stromal layer and appeared to delay its
senescence. Subcultures made in the presence of FGF-4 had up to 10-fold
increases in plating efficiency and grew as relatively uniform monolayers.
These subcultures retained the capacity to support hematopoiesis for
several months, while untreated subcultures, made without FGF-4, grew
erratically and generally lost the capacity to support hematopoiesis within
4 to 6 weeks. The improved growth after subculture greatly enhanced the
reliability of limit- dilution assays of multipotential hematopoietic stem
cells that use stromal cell monolayers. The primary effect of FGF-4
appeared to be on the stromal cells of the long-term bone marrow cultures,
but a direct effect on hematopoietic progenitors could not be ruled out.
Volume 87,
Issue 4,
pp. 1282-1291,
02/15/1996
Copyright © 1996 by The American Society of Hematology
