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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.

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Erfani A, Schieferstein J, Reichert P, Narasimhan C, Pastuskovas C, Parab V Adv Healthc Mater. 2023; 12(15):e2202370.

PMID: 36745878 PMC: 11469019. DOI: 10.1002/adhm.202202370.

References
1.
Olabisi R, Lazard Z, Franco C, Hall M, Kwon S, Sevick-Muraca E . Hydrogel microsphere encapsulation of a cell-based gene therapy system increases cell survival of injected cells, transgene expression, and bone volume in a model of heterotopic ossification. Tissue Eng Part A. 2010; 16(12):3727-36. PMC: 3120095. DOI: 10.1089/ten.TEA.2010.0234. View

2.
Wang D, Gao G . State-of-the-art human gene therapy: part II. Gene therapy strategies and clinical applications. Discov Med. 2014; 18(98):151-61. PMC: 4440458. View

3.
Zhao B, Katagiri T, Toyoda H, Takada T, Yanai T, Fukuda T . Heparin potentiates the in vivo ectopic bone formation induced by bone morphogenetic protein-2. J Biol Chem. 2006; 281(32):23246-53. DOI: 10.1074/jbc.M511039200. View

4.
Baril M, Es-Saad S, Chatel-Chaix L, Fink K, Pham T, Raymond V . Genome-wide RNAi screen reveals a new role of a WNT/CTNNB1 signaling pathway as negative regulator of virus-induced innate immune responses. PLoS Pathog. 2013; 9(6):e1003416. PMC: 3681753. DOI: 10.1371/journal.ppat.1003416. View

5.
Olmsted-Davis E, Gugala Z, Gannon F, Yotnda P, McAlhany R, Lindsey R . Use of a chimeric adenovirus vector enhances BMP2 production and bone formation. Hum Gene Ther. 2002; 13(11):1337-47. DOI: 10.1089/104303402760128568. View