Canine cyclic hematopoiesis (CH) appears to be a disease in which the bone marrow cell renewal oscillates in a 12-day pattern. The proposed studies of CH disease are aimed at studying the marrow's intercellular growth relationships and the marrow cells' responses to humoral regulators. The CH marrow cells will be collected throughout the cycle. Medias conditioned by the cultured marrow will be assessed for their ability: a) to trigger the mouse pluripotential stem cell into DNA synthesis and b) to affect the in vitro growth of erythroid and granulocyte colony forming cells. The medias will also be examined for postaglandin and lactoferrin content. The CH marrows will be separated on the basis of cell density and velocity sedimentation. The separated cell fractions will be assessed for growth in the in vitro erythroid, granulocytic and mixed colony assays in the presence of stimulators (e.g., colony stimulating factors and spleen cell conditioned media) and inhibitors (e.g., prostaglandins and lactoferrins). These studies are aimed at defining interactions between specific cell types and growth modulators. The in vitro clonal assays will also be used to assess the growth of certain cell fractions and recombined cell fractions in the presence and absence of adherent cell components. The Dexter system will be developed to maintain long-term marrow cell cultures from which erythroid, granulocytic and pluripotential stem cells will be measured. Understanding factors that stimulate and inhibit hematopoiesis will contribute to the understanding of many human and animal diseases.
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