The hemopoietic microenvironment of the bone marrow is an essential regulator of in vivo hemopoiesis. In addition to supporting the growth of normal blood cells, it also influences the growth of leukemia. This thesis describes the use of a rat model to examine three aspects of the function of the hemopoietic microenvironment. First, using a myeloid leukemia cell line (BNML), we showed that the pattern of growth of these cells differed in the bone marrow and spleen, that their presence was associated with a relocalization of normal hemopoietic stem cells from marrow to spleen, and that factors (yet to be defined) released from spleen cells altered the pattern, possibly to create a more permissive environment. Second, we showed that the "ST3" marker of marrow fibroblasts was associated with the Thy-1 molecule, and either directly or indirectly contributed to the in vitro adhesion reaction between marrow fibroblastoid cells and normal and leukemic myeloid precursors. Third, we showed that ectopic bony ossicles induced by subcutaneous implantation of recombinant human bone morphogenetic protein-2 contained marrow expressing the full range of hemopoiesis, including stem cells with a potential for long-term repopulation (demonstrated using a rat Y-chromosome specific DNA probe that we developed), and contained fibroblastoid cells differentiated to express the ST3 antigen in a manner similar to those from femoral bone marrow. These results provide further evidence for, although not final proof of, the hypothesis that the ST3 antigen participates in the function of the rat hemopoietic microenvironment, and points the way to future experiments on the interactions between stromal elements and normal and leukemic myeloid precursors.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.41964 |
| Date | January 1996 |
| Creators | An, Jing, 1962- |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Division of Experimental Medicine.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001549375, proquestno: NQ29874, Theses scanned by UMI/ProQuest. |
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