- 2014-12-01 (x)
- Hospitals, Chronic Disease -- statistics & numerical data -- Ohio -- Cleveland (x)
- Bruder, Scott Philip (x)
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Show moreThe present invention provides methods for directing mesenchymal stem cells cultivated in vitro to differentiate into specific cell lineage pathways prior to, or at the time of, their implantation for the therapeutic treatment of pathologic conditions in humans and other species. Mesenchymal stem cells (MSCs) are the formative pluripotent blast or embryonic-like cells found in bone marrow, blood, dermis, and periosteum that are capable of differentiating into specific types of mesenchymal or connective tissues including adipose, osseous, cartilaginous, elastic, muscular, and fibrous connective tissues. The specific differentiation pathway which these cells enter depends upon various influences from mechanical influences and/or endogenous bioactive factors, such as growth factors, cytokines, and/or local microenvironmental conditions established by host tissues. Although these cells are normally present at very low frequencies in bone marrow, a process for isolating, purifying, and mitotically expanding the population of these cells in tissue culture is reported in Caplan et al. U.S. Pat. Nos. 5,197,985 and 5,226,914. In prenatal organisms, the differentiation of MSCs into specialized connective tissue cells is well established; for example embryonic chick, mouse or human limb bud mesenchymal cells differentiate into cartilage, bone and other connective tissues (1-5). In addition, a clonal rat fetus calvarial cell line has also been shown to differentiate into muscle, fat, cartilage, and bone (6). The existence of MSCs in post-natal organisms has not been widely studied with the objective of showing the differentiation of post-embryonic cells into several mesodermal phenotypes. The few studies which have been done involve the formation of bone and cartilage by bone marrow cells following their encasement in diffusion chambers and in vivo transplantation (7, 8). Recently, bone marrow-derived cells from young rabbits (800-1,000 g) have been shown to form adipocytic and osteogenic cells in vivo (9) and cloned bone marrow stromal cells of post-natal mice were shown to form adipocytes and osteogenic cells (10). Likewise, cells from chick periosteum have been isolated, expanded in culture, and, under high density conditions in vitro, shown to differentiate into cartilage and bone (11). Rat bone marrow-derived mesenchymal cells have been shown to have the capacity to differentiate into osteoblasts and chondrocytes when implanted in vivo (12, 6). Cells from various marrow sources of post-natal organisms have never been observed to exhibit myogenic properties, with multinuclear appearance being the most easily recognized characteristic in culture.
http://www.google.com/patents?vid=USPAT5942225
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Show moreThe present invention provides methods for directing mesenchymal stem cells cultivated in vitro to differentiate into specific cell lineage pathways prior to, or at the time of, their implantation for the therapeutic treatment of pathologic conditions in humans and other species. Mesenchymal stem cells (MSCs) are the formative pluripotent blast or embryonic-like cells found in bone marrow, blood, dermis, and periosteum that are capable of differentiating into specific types of mesenchymal or connective tissues including adipose, osseous, cartilaginous, elastic, muscular, and fibrous connective tissues. The specific differentiation pathway which these cells enter depends upon various influences from mechanical influences and/or endogenous bioactive factors, such as growth factors, cytokines, and/or local microenvironmental conditions established by host tissues. Although these cells are normally present at very low frequencies in bone marrow, a process for isolating, purifying, and mitotically expanding the population of these cells in tissue culture is reported in Caplan et al. U.S. Pat. Nos. 5,197,985 and 5,226,914. In prenatal organisms, the differentiation of MSCs into specialized connective tissue cells is well established; for example embryonic chick, mouse or human limb bud mesenchymal cells differentiate into cartilage, bone and other connective tissues (1-5). In addition, a clonal rat fetus calvarial cell line has also been shown to differentiate into muscle, fat, cartilage, and bone (6). The existence of MSCs in post-natal organisms has not been widely studied with the objective of showing the differentiation of post-embryonic cells into several mesodermal phenotypes. The few studies which have been done involve the formation of bone and cartilage by bone marrow cells following their encasement in diffusion chambers and in vivo transplantation (7, 8). Recently, bone marrow-derived cells from young rabbits (800-1,000 g) have been shown to form adipocytic and osteogenic cells in vivo (9) and cloned bone marrow stromal cells of post-natal mice were shown to form adipocytes and osteogenic cells (10). Likewise, cells from chick periosteum have been isolated, expanded in culture, and, under high density conditions in vitro, shown to differentiate into cartilage and bone (11). Rat bone marrow-derived mesenchymal cells have been shown to have the capacity to differentiate into osteoblasts and chondrocytes when implanted in vivo (12, 6). Cells from various marrow sources of post-natal organisms have never been observed to exhibit myogenic properties, with multinuclear appearance being the most easily recognized characteristic in culture.
http://www.google.com/patents?vid=USPAT5736396
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Show moreThe present invention relates to the field of monoclonal antibodies, particularly monoclonal antibodies that are specific for subsets of human osteogenic cells, hybridoma cell lines that synthesize and secrete these antibodies, and the uses of the monoclonal antibodies. Osteogenic cells are responsible for synthesizing and maintaining the extracellular matrix of both embryonic and adult bone. This family, or lineage, of cells arises from undifferentiated mesenchymal stem cells (MSCs) and progresses through a series of distinct maturational stages defined, in part, by the sequential acquisition and/or loss of specific cell surface antigens (Bruder, S. P. and Caplan, A. I., Dev. Biol., 141:319-329,1990). Although monoclonal antibodies against cell surface antigens on normal cells of the osteogenic lineage have been reported for avian and rodent species (Bruder, S. P. and Caplan, A. I., Bone, 10:359-375, 1989; Bruder, S. P. and Caplan, A. I., Bone, 11:189-198, 1990; Turksen, K. et al., J Histochem Cytochem, 40:1339-1352, 1992), none have been reported for human cells. Some of these antibodies reported also react with cells other than those found in bone. While monoclonal antibodies have been raised against intracellular antigens in normal human osteoblasts and against the surface of transformed human osteogenic cell lines, none have recognized the surface of normal human osteoblasts (Embleton, M. J. et al., Br J Cancer, 43:582-587, 1981; Hosoi, S. et al., Cancer Res, 42:654-661, 1982; Heiner, J. et al., Cancer Res, 47:5377-5384, 1987; Bruland, O. et al., Cancer Res, 48:5302-5308, 1988; Tsai, C. et al., Cancer Res, 50:152-161, 1990; Walsh, S. et al., J Bone Miner Res, 9:1687-1696, 1994). At present, the only monoclonal antibody against a cell surface epitope capable of identifying human osteogenic cells is one directed against alkaline phosphatase (Lawson, G. et al., Clin Chem, 31:381-385, 1985). This well-characterized cell surface enzyme has served as the historical standard for identifying a large family of osteogenic cells, and is readily demonstrated by a simple histochemical stain. A common thread highlighted in these studies is the fact that a monoclonal antibody may also react with non-osteogenic cells while remaining a useful marker of osteogenic differentiation. So long as the monoclonal antibody is selective for cells at discrete stages of differentiation, the probe is both novel and useful. In an experimental sense, osteogenic cells have been shown to arise from purified human mesenchymal stem cells in an in vivo setting (Haynesworth, S. E. et al., Bone, 13:81-88, 1992). Mesenchymal stem cells are the formative multipotential blast cells found inter alia in bone marrow, blood, dermis and periosteum that are capable of differentiating into any of the specific types of mesenchymal or connective tissues (i.e. the tissues of the body that support the specialized elements.
http://www.google.com/patents?vid=USPAT5643736
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