The aim of this core is to use a xenotransplantation murine model to provide in vivo readouts for experiments proposed in this program project. Specifically, this model will be used for the following purposes: 1. To optimize proliferation and function of T regulatory cells (Treg) for suppression of alloreactive responses. 2. To perform studies testing the hypothesis that human thymocyte progenitor cells (Tprog) will accelerate human thymopoiesis and peripheral blood T cell responses in immunodeficient mice. 3. To optimize proliferation and function of natural killer (NK) cells for leukemia therapy. These data will in turn inform the design of future clinical trials. The core leader will provide valuable knowledge of the stem cell biology, gene manipulations, murine models, and clinical hematopoietic cell transplantation, all relevant to this application. Core D is unique in its capability to allow two of the three Principal Investigators (who do not have access to preclinical murine models;Project 1 and 3) with a critical shared resource to enhance their scientific program.
Our overall goal is to enhance beneficial effects of cord blood transplantation using subpopulations of immune cells for enhanced lympho-hematopoietic recovery in humanized mice. Investigators in Core D will receive T regulatory, T progenitor and NK cells from investigators in Project 1, 2, and 3, respectively, and evaluate them in immunodeficient mice. These in vivo readouts of cord blood hematopoietic stem cells and additional subsets of human cells will then inform the design of clinical trials.
|Foley, Bree; Felices, Martin; Cichocki, Frank et al. (2014) The biology of NK cells and their receptors affects clinical outcomes after hematopoietic cell transplantation (HCT). Immunol Rev 258:45-63|
|Mitchell, Richard; Wagner, John E; Hirsch, Betsy et al. (2014) Haematopoietic cell transplantation for acute leukaemia and advanced myelodysplastic syndrome in Fanconi anaemia. Br J Haematol 164:384-95|
|Miller, Jeffrey S; Rooney, Cliona M; Curtsinger, Julie et al. (2014) Expansion and homing of adoptively transferred human natural killer cells in immunodeficient mice varies with product preparation and in vivo cytokine administration: implications for clinical therapy. Biol Blood Marrow Transplant 20:1252-7|
|Felices, Martin; Lenvik, Todd R; Ankarlo, Dave E M et al. (2014) Functional NK cell repertoires are maintained through IL-2R? and Fas ligand. J Immunol 192:3889-97|
|Gleason, Michelle K; Ross, Julie A; Warlick, Erica D et al. (2014) CD16xCD33 bispecific killer cell engager (BiKE) activates NK cells against primary MDS and MDSC CD33+ targets. Blood 123:3016-26|
|Kharbanda, Sandhya; Smith, Angela R; Hutchinson, Stephanie K et al. (2014) Unrelated donor allogeneic hematopoietic stem cell transplantation for patients with hemoglobinopathies using a reduced-intensity conditioning regimen and third-party mesenchymal stromal cells. Biol Blood Marrow Transplant 20:581-6|
|Sawitzki, Birgit; Brunstein, Claudio; Meisel, Christian et al. (2014) Prevention of graft-versus-host disease by adoptive T regulatory therapy is associated with active repression of peripheral blood Toll-like receptor 5 mRNA expression. Biol Blood Marrow Transplant 20:173-82|
|Ustun, Celalettin; Bachanova, Veronika; Shanley, Ryan et al. (2014) Importance of donor ethnicity/race matching in unrelated adult and cord blood allogeneic hematopoietic cell transplant. Leuk Lymphoma 55:358-64|
|Kaliyaperumal, Saravanan; Watkins, Benjamin; Sharma, Prachi et al. (2014) CD8-predominant T-cell CNS infiltration accompanies GVHD in primates and is improved with immunoprophylaxis. Blood 123:1967-9|
|Rogosheske, J R; Fargen, A D; DeFor, T E et al. (2014) Higher therapeutic CsA levels early post transplantation reduce risk of acute GVHD and improves survival. Bone Marrow Transplant 49:122-5|
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