We propose to continue studies characterizing the non-hemopoietic stromal cells responsible for stem cell maintenance in long term in-vitro liquid marrow cultures. The two candidate stromal regulator cells which have been isolated by combination of radiation and enzyme digestion will be characterized with regard to antigen constitution, collagen biosynthesis, capacity to produce hemopoietic regulatory factors and to support stem cells in long term liquid culture. Non-irradiated stromal cells will also be evaluated initially utilizing high dose lithium which appears to selectively deplete these marrow cultures of all hemopoietic elements. The mechanism whereby lithium stimulates hemopoiesis will continue to be studied in in vitro liquid culture focusing on the data suggesting that lithium acts via an adherent stromal cell. We will evaluate the effect of lithium on hemopoietic regulatory factor production by irradiated and non-irradiated stromal cells, the cell type on which lithium is acting, and the mechanism underlying the stimulation of stem cells. We will continue studies on the stem cell level at which lithium is acting, concentrating initially on the high proliferative potential stem cell (HPP-CFC) and the day 10 and 14 CFU-S. In a similar manner we will continue investigations of the mechanisms underlying the stimulation of in-vitro Dexter culture hemopoiesis by 5 inches adenosine monophosphate and adenosine. We also plan studies on the mechanism by which lithium causes a late decline in in-vitro hemopoiesis and the effect of lithium on S1/SLD and W/Wv liquid marrow cultures. Lastly, we will continue our efforts to establish a more suitable human (porcine) liquid marrow culture, in order to evaluate features outlined above in these systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK027424-07
Application #
3228302
Study Section
Hematology Subcommittee 2 (HEM)
Project Start
1980-09-01
Project End
1988-08-31
Budget Start
1986-09-01
Budget End
1987-08-31
Support Year
7
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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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