title: Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response.
abstract: 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.
authors.affiliation: 1 Center for Cell and Gene Therapy , Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.
authors.forename: Pedro
authors.initials: P
authors.lastname: Alvarez-Urena
authors.affiliation: 1 Center for Cell and Gene Therapy , Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.
authors.forename: Eleanor
authors.initials: E
authors.lastname: Davis
authors.affiliation: 1 Center for Cell and Gene Therapy , Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.
authors.forename: Corinne
authors.initials: C
authors.lastname: Sonnet
authors.affiliation: 1 Center for Cell and Gene Therapy , Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Henslee
authors.affiliation: 2 Department of Orthopedic Surgery and Rehabilitation, The University of Texas Medical Branch at Galveston , Galveston, Texas.
authors.forename: Zbigniew
authors.initials: Z
authors.lastname: Gugala
authors.affiliation: 2 Department of Orthopedic Surgery and Rehabilitation, The University of Texas Medical Branch at Galveston , Galveston, Texas.
authors.forename: Edward V
authors.initials: EV
authors.lastname: Strecker
authors.affiliation: 2 Department of Orthopedic Surgery and Rehabilitation, The University of Texas Medical Branch at Galveston , Galveston, Texas.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Linscheid
authors.affiliation: 3 Department of Biomedical Engineering, Duke University , Durham, North Carolina.
authors.forename: Maude
authors.initials: M
authors.lastname: Cuchiara
authors.affiliation: 3 Department of Biomedical Engineering, Duke University , Durham, North Carolina.
authors.forename: Jennifer
authors.initials: J
authors.lastname: West
authors.affiliation: 1 Center for Cell and Gene Therapy , Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.|4 Department of Pediatrics-Section Hematology/Oncology, Baylor College of Medicine , Houston, Texas.|5 Department of Orthopedic Surgery, Baylor College of Medicine , Houston, Texas.
authors.forename: Alan
authors.initials: A
authors.lastname: Davis
authors.affiliation: 1 Center for Cell and Gene Therapy , Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas.|4 Department of Pediatrics-Section Hematology/Oncology, Baylor College of Medicine , Houston, Texas.|5 Department of Orthopedic Surgery, Baylor College of Medicine , Houston, Texas.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Olmsted-Davis
mesh_terms: D000256:Adenoviridae; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000276:immunology*; D018914:Cells, Immobilized / Q000276:immunology / Q000637:transplantation; D005347:Fibroblasts / Q000276:immunology / Q000637:transplantation; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011092:Polyethylene Glycols / Q000737:chemistry*; D014161:Transduction, Genetic
chemical_list: C525719:Bmp2 protein, mouse; D055396:Bone Morphogenetic Protein 2; D020100:Hydrogels; C437167:poly(ethylene glycol)diacrylate; D011092:Polyethylene Glycols
keywords: bone formation; cell therapy; in vivo delivery system; priming