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Cellular delivery of TGFβ1 promotes osteoinductive signalling for bone regeneration

2007; Wiley; Volume: 1; Issue: 4 Linguagem: Inglês

10.1002/term.31

1932-7005

Kelly K. Macdonald, Charles Cheung, Kristi S. Anseth,

TGF-β signaling in diseases

Journal of Tissue Engineering and Regenerative MedicineVolume 1, Issue 4 p. 314-317 Short Communication Cellular delivery of TGFβ1 promotes osteoinductive signalling for bone regeneration Kelly K. Macdonald, Kelly K. Macdonald Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USASearch for more papers by this authorCharles Y. Cheung, Charles Y. Cheung Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA The Howard Hughes, University of Colorado, Boulder, CO, USASearch for more papers by this authorKristi S. Anseth, Corresponding Author Kristi S. Anseth kristi.anseth@colorado.edu Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA The Howard Hughes, University of Colorado, Boulder, CO, USAUniversity of Colorado, Department of Chemical and Biological Engineering and Howard Hughes Medical Institute, Campus Box 424, Boulder, CO 80309-0424, USA.Search for more papers by this author Kelly K. Macdonald, Kelly K. Macdonald Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USASearch for more papers by this authorCharles Y. Cheung, Charles Y. Cheung Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA The Howard Hughes, University of Colorado, Boulder, CO, USASearch for more papers by this authorKristi S. Anseth, Corresponding Author Kristi S. Anseth kristi.anseth@colorado.edu Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309-0424, USA The Howard Hughes, University of Colorado, Boulder, CO, USAUniversity of Colorado, Department of Chemical and Biological Engineering and Howard Hughes Medical Institute, Campus Box 424, Boulder, CO 80309-0424, USA.Search for more papers by this author First published: 22 June 2007 https://doi.org/10.1002/term.31Citations: 15AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Abstract Administration of osteoinductive growth factors to wound sites, alone or in conjunction with a delivery vehicle, is an appealing treatment option for critical bone defects. The delivery of cells transfected with genes encoding for osteoinductive growth factors, such as TGFβ1, represents an attractive option to locally deliver constant levels of these growth factors to stimulate new bone formation at the defect site. Using non-viral transfection methods, we showed that osteoblasts can be genetically modified in vitro to secrete sustained therapeutic levels of TGFβ1 in its active form through control of the transfected cell environment. In addition, delivery of TGFβ1 produced by genetically modified cells that contained the proper post-translational modifications provided a more robust cellular response compared to administration of bacterially-derived recombinant TGFβ1. Migration and subsequent proliferation of osteoblasts are critical aspects of the initial steps in the cascade of new bone tissue formation. Exposure to mammalian-derived TGFβ1 induced a more pronounced chemotactic response upon administration of 10 pg/ml TGFβ1, whereas osteoblasts showed enhanced levels of metabolic activity at 100 pg/ml, which is indicative of greater levels of cellular proliferation when compared to addition of the same levels of recombinant TGFβ1. This increased efficacy of cell-derived TGFβ1 over recombinant forms of TGFβ1, combined with provision of a continual source of TGFβ1, highlights the advantages of delivering genetically modified cells over exogenous protein delivery for bone tissue engineering. Copyright © 2007 John Wiley & Sons, Ltd. Citing Literature Volume1, Issue4July/August 2007Pages 314-317 RelatedInformation