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Updated: Aug 2, 2026
A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies
Published on: March 8, 2014
Stimulation of normal rat bone marrow fibroblast proliferation by sera from leukemic Fischer rats
Abstract:
Fibroblast hyperplasia and accumulation of fibrous material in the bone marrow of patients with idiopathic (primary) or secondary myelofibrosis (MF) is believed to result from a reaction by marrow fibroblasts to an altered marrow microenvironment, the alteration being potentiated by abnormal hemic cells. We investigated the hypothesis that humoral factors might contribute to fibroblast overgrowth in MF by using an animal model, aged Fischer rats, where MF frequently occurs with leukemia. Sera from leukemic rats and leukemic cell conditioned media (CM) were assayed for enhancement of normal rat marrow fibroblast proliferation in a culture system where fibroblasts form discrete, adherent colonies. Our results demonstrated that: leukemic sera induced a 170% increase in total fibroblast colony numbers and a 325% increase in colonies containing more than 80 cells, stimulation of fibroblast growth was leukemia related since sera from rats with transplanted leukemia enhanced marrow fibroblast proliferation, leukemic cell CM did not contain a growth factor for marrow fibroblasts, sera from leukemic rats and 2-mercaptoethanol were additive in enhancing marrow fibroblast proliferation and probably act by different mechanisms, and leukemic rat sera was less effective as a colony-stimulating factor than normal rat sera, a condition mimicked when leukemic and normal spleen CM were compared. This is the first time that a serum component has been implicated in the pathogenesis of MF; our work may contribute to understanding the mechanism involved when MF occurs as a complication of leukemia.
Insights
Humoral factors in leukemic rat serum significantly increase fibroblast proliferation, suggesting a role in myelofibrosis development. This finding implicates serum components in the pathogenesis of myelofibrosis associated with leukemia.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- Myelofibrosis (MF) involves fibroblast hyperplasia and fibrous material accumulation in bone marrow.
- This is thought to be a reaction to an altered marrow microenvironment potentiated by abnormal hemic cells.
Purpose of the Study:
- To investigate the hypothesis that humoral factors contribute to fibroblast overgrowth in myelofibrosis.
- To explore the role of serum components in the pathogenesis of MF, particularly when it occurs with leukemia.
Main Methods:
- Used an animal model of aged Fischer rats where MF frequently occurs with leukemia.
- Assayed sera from leukemic rats and conditioned media from leukemic cells for their effect on normal rat marrow fibroblast proliferation in vitro.
- Utilized a culture system where fibroblasts form discrete, adherent colonies.
Main Results:
- Leukemic sera induced a 170% increase in total fibroblast colony numbers and a 325% increase in large colonies (>80 cells).
- Stimulation of fibroblast growth was linked to leukemia, as sera from rats with transplanted leukemia also enhanced proliferation.
- Leukemic cell conditioned media lacked a direct growth factor for marrow fibroblasts.
- Leukemic rat sera and 2-mercaptoethanol showed additive effects on fibroblast proliferation, suggesting different mechanisms of action.
- Leukemic rat sera were less effective as colony-stimulating factors compared to normal rat sera.
Conclusions:
- This study provides the first evidence implicating a serum component in the pathogenesis of myelofibrosis.
- Humoral factors in leukemic sera contribute to fibroblast overgrowth, offering insights into MF mechanisms when it complicates leukemia.
