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Monoclonal antibodies for human osteogenic cell surface antigens (Text)

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  • The 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.
  • 1997-07-01
  • Delphion Inc.,
  • English
  • text
  • text/pdf
  • ksl:casepat-us5643736
Access Rights Open Access
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Case Western Reserve University Patents