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Cellular delivery of TGFβ 1 promotes osteoinductive signalling for bone regeneration
Author(s) -
Macdonald Kelly K.,
Cheung Charles Y.,
Anseth Kristi S.
Publication year - 2007
Publication title -
journal of tissue engineering and regenerative medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.835
H-Index - 72
eISSN - 1932-7005
pISSN - 1932-6254
DOI - 10.1002/term.31
Subject(s) - transfection , microbiology and biotechnology , chemistry , recombinant dna , secretion , transforming growth factor , gene delivery , cell growth , regeneration (biology) , biology , gene , biochemistry
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 TGFβ 1 , 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 TGFβ 1 in its active form through control of the transfected cell environment. In addition, delivery of TGFβ 1 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 TGFβ 1 . 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 TGFβ 1 induced a more pronounced chemotactic response upon administration of 10 pg/ml TGFβ 1 , 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 TGFβ 1 . This increased efficacy of cell‐derived TGFβ 1 over recombinant forms of TGFβ 1 , combined with provision of a continual source of TGFβ 1 , highlights the advantages of delivering genetically modified cells over exogenous protein delivery for bone tissue engineering. Copyright © 2007 John Wiley & Sons, Ltd.