Migration Of Hemopoietic Cells Research Articles

Hepatocyte growth factor/scatter factor (HGF/SF) affects proliferation and migration of myeloid leukemic cells.

Hepatocyte growth factor (HGF), also known as scatter factor (SF), is produced by mesenchymal cells, including bone marrow (BM) stromal cells, and has mitogenic and motogenic effects on a variety of cell types. Recently, a role has been assigned to HGF/SF and its receptor, c-MET, in both normal and malignant hemopoiesis. We investigated the function of HGF/SF on hemopoietic mononuclear cells (MNC) from patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) with circulating blasts. In contrast to results with normal MNC, HGF/SF alone stimulated the proliferation and colony formation of MNC from these patients. MNC from some (4/13) of the AML patients also produced HGF/SF (0.1-0.2 ng/ml/day), while we could not detect HGF/SF in cultures from normal MNC. Furthermore, it appeared that HGF/SF induced migration of leukemic cells in Boyden using KG1a cells as a model for leukemic blasts. The membranes dividing the two compartments of the Boyden chambers were coated with fibronectin. HGF/SF significantly promoted migration in 3/5 samples of MDS patients and in 5/7 samples of AML patients. Supernatant of human BM stromal cells, which is chemoattractive for normal human hemopoietic progenitor cells, also promoted migration of MNC from 4/5 MDS patients and 6/7 AML patients. Since HGF/SF is one of the growth factors produced by BM stromal cells, a neutralizing antibody directed against HGF/SF was added to the BM stroma supernatant, which reduced migration significantly in 2/3 MDS and in 3/6 AML responders to BM stroma supernatant. In conclusion, HGF/SF promotes proliferation and migration of hemopoietic cells from AML and MDS patients in vitro and may therefore contribute to the malignant potential of these cells.

Preferential adhesion of fetal liver derived primitive haemopoietic progenitor cells to bone marrow stroma.

The orderly transfer of haemopoiesis from the fetal liver to the medullary cavities during the ontogeny may result from a decrease in the capacity of the fetal liver to support haemopoiesis. Alternatively it could be facilitated by the preferential migration of primitive haemopoietic cells to the marrow. In this study we have compared the ability of high proliferative potential colony forming cells (HPP-CFC) derived from murine fetal liver (FL) on the 15th day of gestation and from murine adult bone marrow (BM) to adhere to either FL or BM derived stromal layers. Adhesion of FL HPP-CFC to bone marrow stromal layers was significantly greater than all other combinations tested. The remarkable affinity of HPP-CFC derived from FL for BM stromal layers is consistent with the preferential migration of haemopoietic cells from the fetal liver to the medullary cavities.

Differentiation of the mouse hepatic primordium. II. Extrinsic origin of the haemopoietic cell line

The whole hepatic primordium (endoderm + mesenchyme of the septum transversum) was isolated from mouse embryos at various developmental stages, from 8 to 10 days of gestation, and was either grafted into chick or quail embryo or cultivated in vitro. Haemopoiesis developed only if the liver rudiment had been explanted after the 28- to 30-somite stage, but not if explanted prior to this stage, despite normal differentiation of the hepatocytes. However, when the liver rudiment, isolated before the 28-somite stage in in vitro culture, was supplied with exogenous haemopoietic stem cells, haemopoiesis developed in the hepatic tissue. These data show that foetal hepatic haemopoiesis depends on migration of haemopoietic cells which home the liver rudiment at the 28- to 30-somite stage.

Plasminogen activator in the bursa of Fabricius: Correlations with morphogenetic remodeling and cell migrations

The association of controlled extracellular proteolysis, mediated by plasminogen activator, with embryonic tissue remodeling and cell migration was studied in the developing bursa of Fabricius of quail and chick embryos. We found: that the specific activity of plasminogen activator in the bursa changes as a function of developmental age; that these changes are correlated temporally with the migration of hemopoietic cells into the bursal rudiment and with the period of extensive remodeling in the bursal epithelium; that the enzyme is distributed asymmetrically in the epithelial and mesenchymal compartments of the bursa. Chick and quail plasminogen activators can be distinguished by differences in their rates of electrophoretic migration. When interspecific grafts between quail and chick embryos were analyzed in this way, we observed that hemopoietic precursor cells produce plasminogen activator during their colonization of the bursa.

Migration of haemopoietic cells from the yolk sac to the thymus and the bursa of Fabricius in the chick embryo.

The haemopoietic cells of the yolk sac wall of 16‐day‐old chick embryos were locally labelled with 3H‐thymidine in situ. Appropriate controls for the isotope leaking to other parts of the embryo during the local labelling procedure were performed. With autoradiographic technique heavily labelled haemopoietic cells derived from the yolk sac were demonstrated in the thymus and in the bursa of Fabricius 24 hours later. These results directly support the view that the haemopoitic areas of the yolk sac is at least one origin of the lymphoid precursor cells entering the embryonic chick thymus and bursa of Fabricius.