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These cells continuously replicate themselves, while a portion become committed to mesenchymal cell lineages such as bone, cartilage, tendon, legament and muscle. The differentiation of these cells, within each lineage, is a complex multistep pathway involving discrete cellular trasitions much like that which occurs during hematopoiesys. Progression from one stage to the next depends on the presence of specific bioactive factors, nutrients, and other environmental cues whose exquisitely controlled contributions orchestrate the entire differentiation phgenomenon. As understanding of the cellular and molecular events of osteogenic differentiation of MSCs provides the foundation for the emergence of a new therapeutic technilogy for cell therapy. The isolation and in vitro mitotic expansion of autologous human MSCs will support the development of novel protocols for the treatment of many clinically challenging conditions. For example, local bone defects can be repaired through site\u2010directed delivery of MSCs in an appropriate carrier vehicle. Generalized conditions, such as osteoporosis, may be treatable by systemic administration of culture\u2010expanded autologous MSCs or through biopharmaceutical regimens based on the discovery of critical regulatory molecules in the differentiation process. With this in mind, we can begin to explore therapeutic options that have never before been available.<\/jats:p>","DOI":"10.1002\/jcb.240560303","type":"journal-article","created":{"date-parts":[[2005,5,28]],"date-time":"2005-05-28T21:50:14Z","timestamp":1117317014000},"page":"283-294","source":"Crossref","is-referenced-by-count":713,"title":["Mesenchymal stem cells in bone development, bone repair, and skeletal regenaration therapy"],"prefix":"10.1002","volume":"56","author":[{"given":"Scott P.","family":"Bruder","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Fink","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnold 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