Our aim is to define hematopoietic stem cell homing and the impact of cytokine exposure on homing and engraftment after bone marrow transplantation. In addition, we wish to investigate the process of stem cell migration and motility in response to other cells or cytokines and investigate the role of adhesion receptors including integrins in directed movement. We have previously established models for engrafting cells in non-myeloablated and minimally myeloablated murine hosts. We have also studied the effect of different cytokines, most prominently, a combination of interleukeuin-3, interleukin-6, interleukin-11, and steel factor on engraftment of marrow cells in both non-myeloablated and myeloablated hosts. We have found that such cytokine exposure in liquid culture over 48 hours leads to a fluctuation engraftment phenotype with loss of engraftment in late S/early G2 phases of cell cycle and return in G1. Lastly, we have defined numerous adhesion receptors critical to the interaction of stem cell populations with stromal cells in vitro, an determined how cytokines modulate adhesion receptor expression and function. The present grant focuses on defining mechanisms of homing of bone marrow stem cells using fluorescent labels over the first 20 hours of engraftment. A second major aims is to evaluate the impact of cytokine alterations on homing and presumably, adhesion receptor expression. Lastly, we have begun to evaluate in vitro surrogate models of homing looking at stem cell binding to Dexter cultures and visualization using inverted fluorescence and deconvolution fast microscopy of fluorescent labeled highly purified Lin- rho(lo)ho(lo) and Lin-Scn+ murine stem cells isolated by MoFlo high speed sorting. We plan to continue these studies with a focus on the lamellipodial projects from these stem cells and define the distribution and functional role of adhesion receptors including integrins in cell adhesion, cell motility, and directed cell migration. The influence of cytokines on the appearance, localization, and function of cell processes and distribution of adhesion receptors on both stem cells and stromal cells will also be examined.
| 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 |
| 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 |
| Nowakowski, Grzegorz S; Dooner, Mark S; Valinski, Helen M et al. (2004) A specific heptapeptide from a phage display peptide library homes to bone marrow and binds to primitive hematopoietic stem cells. Stem Cells 22:1030-8 |
| Dooner, Mark; Cerny, Jan; Colvin, Gerald et al. (2004) Homing and conversion of murine hematopoietic stem cells to lung. Blood Cells Mol Dis 32:47-51 |
| Quesenberry, Peter J; Abedi, Mehrdad; Aliotta, Jason et al. (2004) Stem cell plasticity: an overview. Blood Cells Mol Dis 32:1-4 |
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