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Experimental Analysis of Developing Hemopoiesis in Fetal Bone Marrow

Extract: 1. We have used fetal rats to study the following aspects of the development of hemopoiesis: (a) content of hemopoietic stem cells in fetal bone marrow, liver, and peripheral blood and (b) origin of hemopoietic cells in the developing mammalian bone marrow.2. In the studies we utilized the diffusion chamber technique to study the content of stem cells committed to granulopoiesis. The number of myelopoietic stem cells in liver peripheral blood and in “bone marrow” of 18-day-old rats is nearly identical. Since in “bone marrow” a considerable number of peripheral blood cells are present in the vessels at that time, whereas extravascular cells consist only of mesenchymal cells, one might assume that these periph- eral blood cells give rise to granulocytic precursors in the cultures. Morphologically these cells are “blast” cells and lymphocytes.3. Based on cell labeling indices of radioautograms, derived from continuous infusion of pregnant rats with [3H]thymidine, it could be shown that in the perichondral area mesenchymal cells of the fetus and newborn have a slow rate of DNA turnover whereas “bone marrow” cells are in an active state of profileration.4. In further support of this it was also shown that injections of hydroxyurea (an agent which destroys cells in DNA synthesis) has virtually no effect on perichondral mesenchymal cells whereas “bone marrow” cells were completely hlocked in their ability to sup- port myelopoietic differentiation in the diffusion chamber implants.5. The conclusions would therefore be that (a)local perichondral cells, i.e., mesenchymal cells, do not contribute to marrow hemo- poiesis, (b)matrix cells of the developing bone marrow cannot reconstitute hemopoiesis, and (c)hemopoietic bone marrow cells develop from migrating peripheral “stem cells,” one of the sources being the liver.Speculation: The development of mammalian bone marrow hemopoiesis is initiated by circulating blood stem cells. The blood receives the stem cells at this time of development mainly from the liver. The morphology of the expanding stem cell population in embryogenesis varies between small mononuclearlymphocyte-like cells and “blast” cells.