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In vitro functions of stromal cells from human and mouse bone marrow
Abstract:
Human fibroblastoid cell strains obtained from primary bone marrow cultures and continuous stromal cell lines recently derived from mouse bone marrow were studied. The incidence of fibroblastoid precursors (CFU-F) varied considerably in human bone marrow samples, and no differences could be detected between marrows from a group of myelodysplastic patients (age range 70-82 years) and groups of age-matched controls or younger individuals. A lack of direct correlation between initial clonogenicity and ultimate capacity of fibroblastoid cells to grow in continuous culture was observed in both the normal and the myelodysplastic groups. Despite the apparently normal clonogenicity of CFU-F in patients with myelodysplastic syndromes, some of these marrows failed to grow when subcultured. Normal fibroblastoid cells at 10(4) per culture exhibited myelopoietic activities when cocultured with fresh bone marrow cells. At higher concentrations, these cells inhibited myeloid colony formation. Fibroblastoid cells from only one out of four myelodysplastic patients examined exhibited comparable inhibitory activity. The specificity of the inhibitor(s) was demonstrated by the lack of effect of fibroblastoid cells from normal human bone marrow on the clonogenicity of mouse erythroleukemia cells. Moreover, human foreskin fibroblasts were devoid of such inhibitory activity. These functions of cultured stromal cells may correlate with some of their activities in the bone marrow microenvironment.
Insights
Human bone marrow stromal cells, including fibroblastoid precursors (CFU-F), show normal initial growth in myelodysplastic syndromes. However, some exhibit impaired long-term growth and altered inhibitory functions, suggesting microenvironment dysregulation.
Area of Science:
- Hematology
- Cell Biology
- Oncology
Background:
- Bone marrow stromal cells, including fibroblastoid precursors (CFU-F), are crucial for hematopoiesis.
- Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and a risk of transformation to acute myeloid leukemia.
- The role of stromal cell function in MDS pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the characteristics and function of human and mouse bone marrow fibroblastoid cells in normal and myelodysplastic conditions.
- To assess the clonogenicity and long-term growth potential of fibroblastoid precursors (CFU-F) in MDS patients.
- To evaluate the myelopoietic and inhibitory activities of cultured stromal cells.
Main Methods:
- Isolation and culture of human and mouse bone marrow fibroblastoid cells.
- Assessment of fibroblastoid precursor (CFU-F) incidence and clonogenicity.
- Co-culture experiments with fresh bone marrow cells to evaluate myelopoietic and inhibitory activities.
- Testing the effect of fibroblastoid cells on mouse erythroleukemia cells and human foreskin fibroblasts to determine specificity.
Main Results:
- Fibroblastoid precursor (CFU-F) incidence in human bone marrow did not differ between MDS patients and controls.
- A lack of correlation between initial clonogenicity and long-term growth capacity was observed in both normal and MDS groups.
- Normal fibroblastoid cells exhibited myelopoietic activity and inhibition of myeloid colony formation at higher concentrations, while MDS-derived cells showed reduced inhibitory activity.
Conclusions:
- Despite normal initial clonogenicity, fibroblastoid cells from some MDS patients exhibit impaired long-term growth and altered regulatory functions.
- These findings suggest potential dysregulation of the bone marrow microenvironment in MDS.
- Cultured stromal cell functions may reflect their in vivo roles within the bone marrow microenvironment.