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

Pedro Alvarez-Urena, Eleanor Davis, Corinne Sonnet, Gabrielle Henslee, Zbigniew Gugala, Edward V. Strecker, Laura J. Linscheid, Maude Cuchiara, Jennifer West, Alan Davis, Elizabeth Olmsted-Davis

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)177-184
Number of pages8
JournalTissue Engineering - Part A
Volume23
Issue number5-6
DOIs
StatePublished - Mar 1 2017

Fingerprint

Bone Morphogenetic Protein 2
Hydrogels
Viruses
Encapsulation
Adenoviridae
Osteogenesis
Polyethylene glycols
Bone
Hydrogel
Gene therapy
Proteins
Neutralizing Antibodies
Intramuscular Injections
Animals
Immunity
Antibodies
Inbred NOD Mouse
SCID Mice
poly(ethylene glycol)diacrylate
Inbred C57BL Mouse

Keywords

  • bone formation
  • cell therapy
  • in vivo delivery system
  • priming

ASJC Scopus subject areas

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response. / Alvarez-Urena, Pedro; Davis, Eleanor; Sonnet, Corinne; Henslee, Gabrielle; Gugala, Zbigniew; Strecker, Edward V.; Linscheid, Laura J.; Cuchiara, Maude; West, Jennifer; Davis, Alan; Olmsted-Davis, Elizabeth.

In: Tissue Engineering - Part A, Vol. 23, No. 5-6, 01.03.2017, p. 177-184.

Research output: Contribution to journalArticle

Alvarez-Urena, P, Davis, E, Sonnet, C, Henslee, G, Gugala, Z, Strecker, EV, Linscheid, LJ, Cuchiara, M, West, J, Davis, A & Olmsted-Davis, E 2017, 'Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response', Tissue Engineering - Part A, vol. 23, no. 5-6, pp. 177-184. https://doi.org/10.1089/ten.tea.2016.0277
Alvarez-Urena, Pedro ; Davis, Eleanor ; Sonnet, Corinne ; Henslee, Gabrielle ; Gugala, Zbigniew ; Strecker, Edward V. ; Linscheid, Laura J. ; Cuchiara, Maude ; West, Jennifer ; Davis, Alan ; Olmsted-Davis, Elizabeth. / Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response. In: Tissue Engineering - Part A. 2017 ; Vol. 23, No. 5-6. pp. 177-184.
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