The nature and function of fibroblastoid reticular cells in the hemopoietic stroma

textabstractThe experimental work of this thesis, described in the appendix papers, is aimed at characterization of the nature and function of fibroblastic reticular cells in the hemopoietic stroma. A number of experimental models was employed to elucidate different aspects of these cells. In the first appendix paper characteristics are described of fibroblastoid colony-forming cells (CFU-F) from murine bone marrow and their in yitro progeny. The data indicate that these fibroblastoid cells differ frorrlm~ phages and endothelial cells, and can be discriminated from fibroblastoid cells from other organs. The second appendix paper describes three monoclonal antibodies that specifically recognize a determinant on non-phagocytic and phagocytic reticular eel ls in the hemopoietic stroma of fetal and adult mice. Reticular stromal cells with this specific determinant(s) are restricted to sites of adulttype hemopoiesis. In the third appendix paper the regulatory capacity of a spleen-derived fibroblastoid cell line on in vitro myelopoiesis is described. This cell line is shown to produce two solUble regulators and one cell-associated activity by which in vitro myelopoiesis is modulated. The fourth appendix paper describes the transplantabil ity of CFU-F after lethal total body irradiation and bone marrow transplantation. Evidence is presented indicating that CFU-F can efficiently lodge in the recipients bone marrow. The fifth appendix paper represents a study of the long-term recovery of CFU-F after lethal total body irradiation and bone marrow transplantation. This recovery is slow and incomplete, independent of graft size and presence of adherent stromal cells in the graft. If present in the graft, donor stromal cells do contribute to the recipients stroma. but they do not influence the total CFU-F recovery. Subsequent treatment with a sublethal dose of endotoxin allows full recovery of the CFU-F population. The sixth appendix paper describes the kinetics of hemopoietic and stromal cells in phenylhydrazine-treated mice. In addition, evidence is presented that under these conditions CFU-F migrate into spleen and bone marrow via the blood stream. In the seventh appendix paper a strong correlation is described between CFU-F numbers and the regenerative capacity of ectopically transplanted stroma in femurs of mice treated with several doses of gamma irradiation