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 language | English (US) |
|---|---|
| Pages (from-to) | 177-184 |
| Number of pages | 8 |
| Journal | Tissue Engineering - Part A |
| Volume | 23 |
| Issue number | 5-6 |
| DOIs | |
| State | Published - Mar 1 2017 |
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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 journal › Article
}
TY - JOUR
T1 - Encapsulation of Adenovirus BMP2-Transduced Cells with PEGDA Hydrogels Allows Bone Formation in the Presence of Immune Response
AU - Alvarez-Urena, Pedro
AU - Davis, Eleanor
AU - Sonnet, Corinne
AU - Henslee, Gabrielle
AU - Gugala, Zbigniew
AU - Strecker, Edward V.
AU - Linscheid, Laura J.
AU - Cuchiara, Maude
AU - West, Jennifer
AU - Davis, Alan
AU - Olmsted-Davis, Elizabeth
PY - 2017/3/1
Y1 - 2017/3/1
N2 - 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.
AB - 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.
KW - bone formation
KW - cell therapy
KW - in vivo delivery system
KW - priming
UR - http://www.scopus.com/inward/record.url?scp=85014588981&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85014588981&partnerID=8YFLogxK
U2 - 10.1089/ten.tea.2016.0277
DO - 10.1089/ten.tea.2016.0277
M3 - Article
C2 - 27967655
AN - SCOPUS:85014588981
VL - 23
SP - 177
EP - 184
JO - Tissue Engineering - Part A.
JF - Tissue Engineering - Part A.
SN - 1937-3341
IS - 5-6
ER -