Abstract: Hematopoietic stem cells are extremely difficult to maintain or expand in vitro. Two observations in traditional long-term bone marrow cultures strongly suggest that macrophages may be at the root of the problem: First, micromolar concentrations of hydrocortisone improve the longevity of long-term bone marrow cultures and hydrocortisone is known as a potent inhibitor of macrophage production of pro-inflammatory cytokines, chemokines, enzymes, nitrogen oxide and reactive oxygen species and redirects macrophages to the anti-inflammatory differentiation pathway; Second, the decline of hematopoiesis in long-term bone marrow cultures coincides with the development of large numbers of adherent and non-adherent macrophages including foreign body giant cells. These adherent macrophages and foreign body giant cells exhibit well-spread morphology, contain numerous lysosomes and phagolysosomes in the cytoplasm and are metabolically active.

Abstract: Hematopoietic stem cells are extremely difficult to maintain or expand in vitro. Two observations in traditional long-term bone marrow cultures strongly suggest that macrophages may be at the root of the problem: First, micromolar concentrations of hydrocortisone improve the longevity of long-term bone marrow cultures and hydrocortisone is known as a potent inhibitor of macrophage production of pro-inflammatory cytokines, chemokines, enzymes, nitrogen oxide and reactive oxygen species and redirects macrophages to the anti-inflammatory differentiation pathway; Second, the decline of hematopoiesis in long-term bone marrow cultures coincides with the development of large numbers of adherent and non-adherent macrophages including foreign body giant cells. These adherent macrophages and foreign body giant cells exhibit well-spread morphology, contain numerous lysosomes and phagolysosomes in the cytoplasm and are metabolically active.

Abstract: Penumbra is the newest member of the tetraspanin superfamily of membrane proteins. A major obstacle in penumbra research has been the lack of monoclonal antibodies against the native penumbra. In this invention, we detail the establishment and characterization of monoclonal antibodies that recognize both human and mouse penumbras on living cells. Furthermore, we created chimeric mouse-human IgG1 antibodies from these mouse monoclonal antibodies. Using these antibodies, we demonstrate for the first time that penumbra is expressed on the surface of virtually all CD19+ or CD20+ B lymphocytes in blood, bone marrow, spleen and lymph nodes. In vivo, these monoclonal antibodies shrank lymphoid follicles in spleen. Thus, these antibodies establish penumbra as a novel B cell marker with a wider range of expression level than CD19 or CD20. These monoclonal antibodies pave the way for new research and potential therapeutic applications in immunology, hematology and oncology.

Abstract: The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.

Abstract: The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.

Abstract: The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.

Abstract: The present invention relates to murine and human Penumbra (for proerythroblast nu[new] Membrane) nucleic acid molecules, proteins and the uses thereof. The invention further relates to the use of Penumbra molecules for the detection of 7q31q32-related deletions, including such deletions associated with myeloid malignancies, particularly detection by hybridization using Penumbra-based probes.

Abstract: The invention relates to natural killer cells and methods for the development of immortalized natural killer cells and use of the natural killer cells. A growth and culture system is described that supports increased natural killer cell development, and provides for the establishment of continuous natural killer cell lines. Additionally, the disclosed method for generating natural killer cells may be used to produce large numbers of natural killer cells for therapeutic applications and for natural killer cell research.

Abstract: Methods for establishing continuous SCF dependent lympho-hematopoietic progenitor cell lines capable of differentiating into erythroid, myeloid, and B lymphocytic lineages, and GM-CSF dependent neutrophil progenitor cell lines capable of differentiating into neutrophils but not into monocytes, mast cells, or basophils, by introducing into bone marrow, fetal spleen, fetal liver, or other hematopoietic myeloid cells nucleic acid encoding a dominant negative suppressor of a retinoic acid receptor-alpha and a selectable marker, and culturing the recombinant cells in culture medium containing SCF or GM-CSF, agents allowing for selective growth of the recombinant cells, and a level of retinoic acid of less than about 10.sup.-8 M to about 10.sup.-9 M in the case of establishing neutrophilic progenitor cell lines. Addition of a retinol compound induces the latter cell line to differentiate into neutrophils.