<span>The 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 </span><span>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</span>

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