Factors required for bone marrow stromal fibroblast colony formation in vitro

Marrow stromal fibroblasts (MSFs) are essential for the formation of the haemopoietic microenvironment and bone; however, regulation of MSF proliferation is poorly understood. MSF colony formation was studied in primary mouse and human marrow cell cultures. After a brief exposure to serum, MSF colon...

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Bibliographic Details
Published in:British journal of haematology 1997-06, Vol.97 (3), p.561-570
Main Authors: Kuznetsov, Sergei A., Friedenstein, Alexander J., Gehron Robey, Pamela
Format: Article
Language:English
Subjects:
Adolescent
Adult
Animals
Bone Marrow Cells
Cell Division
Child
Child, Preschool
colony formation
Culture Media, Serum-Free
Fibroblasts - cytology
growth factors
Growth Substances - physiology
Guinea Pigs
Humans
marrow stromal fibroblasts
Mice
Mice, Inbred Strains
Middle Aged
neutralizing antibodies
Stem Cells - cytology
Stromal Cells - cytology
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Summary:Marrow stromal fibroblasts (MSFs) are essential for the formation of the haemopoietic microenvironment and bone; however, regulation of MSF proliferation is poorly understood. MSF colony formation was studied in primary mouse and human marrow cell cultures. After a brief exposure to serum, MSF colony formation occurred in the absence of both serum and non‐adherent marrow cells, if medium conditioned by marrow cells was present (serum‐free conditioned medium, SF‐CM). In mouse and human cultures stimulated to proliferate by SF‐CM, neutralizing antibodies against PDGF, TGF‐β, bFGF and EGF specifically suppressed MSF colony formation. The degree of supression was species‐dependent, with the most profound inhibition achieved in mouse cultures by anti‐PDGF, anti‐bFGF and anti‐EGF, and in human cultures by anti‐PDGF and anti‐TGF‐β. Serum‐free medium not conditioned by marrow cells (SFM) did not support MSF colony formation. In mouse cultures in SFM, human recombinant bFGF and bovine natural bFGF were able to partially substitute for the stimulating effect of SF‐CM. Other growth factors, including TGF‐β1, TGF‐β2, PDGF, EGF, IL‐6, IGF‐I and IGF‐II, showed no activity when tested alone. In human cultures in SFM, none of the growth factors, alone or in combination, stimulated MSF colony formation. Mouse and human MSFs grown in SF‐CM formed bone and a haemopoietic microenvironment when transplantated into immunodeficient mice in vivo, and therefore were functionally equivalent to MSFs generated in the presence of serum. These data indicate that stimulation of the initial proliferation of an MSF precursor cell is complex, and requires participation of at least four growth factors: PDGF, bFGF, TGF‐β and EGF. In addition, mouse and human MSF precursor cells have different requirements for each of the growth factors.
ISSN:0007-1048
1365-2141
DOI:10.1046/j.1365-2141.1997.902904.x