Control of the timing and dosage of IGF-I delivery from encapsulated cells.
We report here on the development and characterization of a cell-based system for the regulated delivery of bioactive insulin-like growth factor I (IGF-I). A stable mammalian cell line, CHO-K1 Tet-IGFI, was genetically modified to have tetracycline-induced transcription of the human IGF-I gene. Cells were activated to express IGF-I in the presence of doxycycline (DOX), a tetracycline derivative, while expression was inactivated in the absence of DOX. Temporal, or on-off, release of IGF-I from cells encapsulated within Ca²⁺-alginate hydrogels was demonstrated in a pilot study over the course of 10 days in culture. Released growth factor was bioactive, exhibiting a proliferative effect comparable to recombinant purified IGF-I protein. The dosage levels and temporal control of IGF-I release from encapsulated cells meet the requirements of orthopedic wound repair, making this approach an attractive means for the controlled synthesis and delivery of growth factors in situ for wound healing.
Center for Biomedical Engineering, Brown University, 171 Meeting Street, Providence, Rhode Island 02906, USA. roshni.patel@gmail.com
Roshni S
RS
Patel
Amy
A
Chang
Michael J
MJ
Lysaght
Jeffrey R
JR
Morgan
D000818:Animals; D001681:Biological Assay; D016466:CHO Cells; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018914:Cells, Immobilized / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D004305:Dose-Response Relationship, Drug; D004318:Doxycycline / Q000494:pharmacology; D016503:Drug Delivery Systems; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage* / Q000494:pharmacology*; D061986:MCF-7 Cells; D013696:Temperature; D013752:Tetracycline / Q000494:pharmacology; D013997:Time Factors
D007334:Insulin-Like Growth Factor I; D013752:Tetracycline; D004318:Doxycycline