Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response

Autor: Edward V. Strecker, Alan R. Davis, Pedro Alvarez-Urena, Eleanor L. Davis, Gabrielle Henslee, Corinne Sonnet, Elizabeth A. Olmsted-Davis, Jennifer L. West, Maude L. Cuchiara, Laura J. Linscheid, Zbigniew Gugala
Rok vydání: 2017
Předmět:
Zdroj: Tissue Engineering Part A. 23:177-184
ISSN: 1937-335X
1937-3341
DOI: 10.1089/ten.tea.2016.0277
Popis: Gene therapy approaches have been difficult to implement due to pre-existing immunity against the virus used for delivery. To circumvent this problem, a cell-based approach was developed that avoided the use of free virus within the animal. However, even cells transduced in vitro with E1- to E3-deleted adenovirus encoding bone morphogenetic protein 2 (AdBMP2) resulted in the production of virus-neutralizing antibodies in mice. Furthermore, when mice received an intramuscular injection of nonencoding adenovirus (AdEmpty)-transduced cells, AdBMP2-transduced cells were unable to launch bone formation when an intramuscular injection of these BMP2-producing cells was delivered 1 week later. This phenomenon was not observed in NOD/SCID mice, and could be overcome in C57BL/6 mice by encapsulating the adenovirus-transduced cells in a nondegradable hydrogel poly(ethylene glycol) diacrylate (PEGDA). Data collectively suggest that PEGDA hydrogel encapsulation of AdBMP2-transduced cells prevents pre-existing immunity from suppressing BMP2-induced bone formation.
Databáze: OpenAIRE