It is aimed at generating new insights into stem cell physiology and increasing donor availability and safety by achieving engraftment in the absence of graft vs. host disease (GVHD) with dog leukocyte antigen (DLA) haploidentical and matched donor cells. The second area is aimed at understanding the mechanisms whereby growth factors can modify the effects of total body irradiation on production of granulocytes and plateletes.
The specific aims are: (1) define the phenotypes of canine hematopoietic progenitors present in the peripheral blood mobilized with growth factors and assay their in vitro and in vivo functions; 2) establish successful stem cell grafts without GVHD in canine litermates which are genotopically DLA-identical or are DLA-haploidentical with the cell donor; and 3) identify which growth factors or combinations are most effective I modifying marrow toxicity of total body irradiation and define the mechanisms responsible for this activity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK042716-09
Application #
2905418
Study Section
Hematology Subcommittee 2 (HEM)
Program Officer
Badman, David G
Project Start
1990-04-01
Project End
2002-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
9
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Fred Hutchinson Cancer Research Center
Department
Type
DUNS #
075524595
City
Seattle
State
WA
Country
United States
Zip Code
98109
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Georges, George E; Lesnikov, Vladimir; Baran, Szczepan W et al. (2010) A preclinical model of double- versus single-unit unrelated cord blood transplantation. Biol Blood Marrow Transplant 16:1090-8
Abrams, V Kraig; Hwang, Billanna; Lesnikova, Marina et al. (2010) A novel monoclonal antibody specific for canine CD25 (P4A10): selection and evaluation of canine Tregs. Vet Immunol Immunopathol 135:257-65
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Sangiolo, D; Lesnikova, M; Nash, R A et al. (2007) Lentiviral vector conferring resistance to mycophenolate mofetil and sensitivity to ganciclovir for in vivo T-cell selection. Gene Ther 14:1549-54
Baron, Frederic; Storb, Rainer (2006) The immune system as a foundation for immunologic therapy and hematologic malignancies: a historical perspective. Best Pract Res Clin Haematol 19:637-53
Baron, F; Sandmaier, B M (2006) Chimerism and outcomes after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Leukemia 20:1690-700
Yunusov, Murad Y; Kuhr, Christian S; Georges, George E et al. (2006) Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft. Transplantation 82:629-37
Baron, Frederic; Little, Marie-Terese; Storb, Rainer (2005) Kinetics of engraftment following allogeneic hematopoietic cell transplantation with reduced-intensity or nonmyeloablative conditioning. Blood Rev 19:153-64
Baron, Frederic; Sandmaier, Brenda M (2005) Current status of hematopoietic stem cell transplantation after nonmyeloablative conditioning. Curr Opin Hematol 12:435-43

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