Bone marrow stromal cell factor production appears to be a critical aspect of regulating in vivo hemolymphopoiesis. The long-term objective of this grant is to define the nature of stromal derived growth factors both from murine (and human) species involved in the regulation of hemopoiesis with a particular emphasis on actions on early multilineage, stem cells.
The specific aims i nvolve the study of the nature of hemolymphopoietic growth factors produced by isolated murine myeloid and lymphoid long term culture adherent cells and the effects of growth factor production of exposure to various inducers including lithium, lectins, phorbol esters, interleukin-l, endotoxin, calcium ionophores and different accessory cells. The growth factors are to be characterized by bioassay, biochemistry and mRNA production and stability. Control of stromal growth factor production will also be assessed at the mRNA level with long-term goals of evaluating possible DNA binding proteins or transacting factors controlling growth factor production. We also plan to assess the role of local conditions in regulating growth factor production from """"""""lymphoid"""""""" stroma and """"""""myeloid'' marrow stroma. These studies will address a full evaluation of the nature of the adherent cells in murine myeloid (Dexter) and lymphoid (Whitlock-Witte) long-term marrow cultures and directly assess whether or not two major candidate stromal regulatory cells, a macrophage and the alkaline phosphatase positive preadipocyte fibroblasts, derive from a common progenitor cell. Lastly, studies are designed to address an in vivo model of endotoxin myeloid stimulation attempting to understand the potential role of early acting growth factors in this model. These studies should lead to a more complete understanding of the regulation of early myeloid and lymphoid stem cells and may lead to the possible identification of unique stromal derived growth factors. The latter type of growth factors could potentially be utilized in the therapy of myelodeficiency states or in attempts to induce leukemic cell differientiation while a fuller understanding of the regulation of hemolymphopoiesis may impact upon diseases such as aplastic anemia and leukemia and on chemotherapy induced cytopenias.
| Colvin, Gerald A; Berz, David; Liu, Liansheng et al. (2010) Heterogeneity of non-cycling and cycling synchronized murine hematopoietic stem/progenitor cells. J Cell Physiol 222:57-65 |
| Aliotta, Jason M; Keaney, Patrick; Passero, Michael et al. (2006) Bone marrow production of lung cells: the impact of G-CSF, cardiotoxin, graded doses of irradiation, and subpopulation phenotype. Exp Hematol 34:230-41 |
| Quesenberry, Peter J; Colvin, Gerald; Abedi, Mehrdad (2005) Perspective: fundamental and clinical concepts on stem cell homing and engraftment: a journey to niches and beyond. Exp Hematol 33:9-19 |
| Quesenberry, Peter J; Colvin, Gerald A; Abedi, Mehrdad et al. (2005) The stem cell continuum. Ann N Y Acad Sci 1044:228-35 |
| Quesenberry, Peter J; Abedi, Mehrdad; Aliotta, Jason et al. (2004) Stem cell plasticity: an overview. Blood Cells Mol Dis 32:1-4 |
| Cerny, Jan; Quesenberry, Peter J (2004) Chromatin remodeling and stem cell theory of relativity. J Cell Physiol 201:1-16 |
| Lum, Lawrence G; Fok, Hubert; Sievers, Richard et al. (2004) Targeting of Lin-Sca+ hematopoietic stem cells with bispecific antibodies to injured myocardium. Blood Cells Mol Dis 32:82-7 |
| D'Hondt, Lionel; McAuliffe, Christina; Damon, Jeffrey et al. (2004) Circadian variations of bone marrow engraftability. J Cell Physiol 200:63-70 |
| Colvin, G A; Lambert, J-F; Abedi, M et al. (2004) Murine marrow cellularity and the concept of stem cell competition: geographic and quantitative determinants in stem cell biology. Leukemia 18:575-83 |
| Colvin, Gerald A; Lambert, Jean-Francois; Abedi, M et al. (2004) Differentiation hotspots: the deterioration of hierarchy and stochasm. Blood Cells Mol Dis 32:34-41 |
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