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COLONY GROWTH AND GRANULOPOIETIC EFFECTS OF HUMAN BONE MARROW FIBR.OBL.AST COLONY-FORMING CELLS IN VITRO
Abstract:Human bone marrow derived fibroblast colony- ;forming cells (F-CFU) and granulocytemacrophage colony-forming cells (GM-CFU) were simultaneously studied by liquid and semi-solid agar culture in 26 normal individuals and 33 hematological disorders iii 13 patients with aplastic anemia, 9 acute non lymphocytic leukemia, 6 acute Iymphocytic leukemia and 5 malignant lymphoma. After 2 weeks of liquid culture, the growth rates and morphological charac teristics of F-CFU from aplastic and leukemic mar rows did not differ markedly from the normal, except that patient groups show a wider range of colony number. The F-CFU incidence in patients with malignant lymphoma was lower than normal. Growth of GM-CFU from patients with aplastic anemia and Ieukemia was very poor. GM-CFU stimulation was not detected iii any supernatants of F-CFU cultures. Confluent mono layers of fibroblast cells grown from normal and aplastic marrow could directly stimulate the growth cf GM-CFU of normal marrow cells and little GM- CFU was observed in areas lacking fibroblast cells. Fibroblast monolayers derived from acute leukemic marrows were poor stimulators of GM-CFU, this abnormality in interactions between stromal cells and hematopoietic progenitors may be important in the pathogenesis and clinical manifestation of leukemia. This study suggests that bone marrow fibroblast cells may directly affect hematopoietic stem cell proliferation and differentiation and supports the hypothesis that marrow fibrosis observed in patients with leukemia is of non-ncoplastic origin and may be a reactive phenomenon. Analysis of the pathoge- nesis of aplastic patients with defective hematopoie tic microenvironments may be possible.
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