Bone marrow adherent cell hemopoietic growth factor production

Abstract

These data suggest that two types of radioresistant adherent stromal cells are adequate for maintenance of long term hemopoiesis in the Dexter culture system. One cell type appears to be a typical adherent macrophage while the other is an alkaline phosphatase positive epitheloid cell possibly representative of the adventitial reticular cell of the bone marrow. These two cell types seem to be clearly defined by the in-vivo irradiation studies and less clearly defined in the in-vitro irradiation experiments. These data do not exclude other cell types as playing important roles in modulating hemopoiesis but do suggest that these major types are probably playing important roles in maintaining stem cells in long term liquid cultures. In addition, data suggests that the epitheloid cell directly nurtures hemopoietic cells on its surface while the macrophages may serve a separate function. A number of growth factors are produced by these two cell types which appear to include CSF-1, a granulocyte CSA separate from CSF-1 and a megakaryocyte CSA separate from both the GM-CSA and CSF-1 (Table 5). Thus the present data suggest that there are at least three (formula; see text) separate hemopoietic growth factors produced. The FDC-P1 activity produced by irradiated stroma would appear most likely to be GM-CSA-II. The fact that lectins enhanced production of these activities is intriguing but the cell type on which the lectins are acting has not as yet been defined. It appears that lithium also acts upon adherent marrow stromal cells to induce production of myeloid regulatory growth factors. Lithium appears to stimulate both normal and irradiated stroma to produce hemopoietic maintenance and growth factors and the present data suggests that factors active on pre IL-3 cells, HPP-CFC, CFU-D, CFU-meg, and CFU-S are all induced from these stromal cells by lithium. Whether the lithium induced factors and the factors derived from irradiated stroma represent a number of different growth factors or one or two critical regulatory molecules is at present unclear. The synergistic activity derived from the TC-1 cell line is of particular interest in this regard. This CSF-1 dependent activity is capable of acting on a very primitive stem cell to induce impressive proliferation and differentiation. In addition an activity in TC-1 conditioned media which may be synergistic activity appears capable of inducing adherent marrow cell lines which then can subsequently produce more of the same factor, a classic autocrine system.(ABSTRACT TRUNCATED AT 400 WORDS)