Increased transduction of human intestinal epithelial cells by adenoviral vectors in inflammatory bowel disease.
BACKGROUND
Delivery of genes encoding anti-inflammatory proteins has been proposed as a strategy for the treatment of inflammatory bowel disease (IBD). The goal of this study was to assess the ability of a standard adenoviral vector to transfect epithelial cells in intestinal explants from patients with IBD compared with controls.


METHODS
Endoscopic colon biopsies obtained from patients with no history of IBD and endoscopically normal colon (n = 4), patients with a history of ulcerative colitis (UC; n = 5), and patients with a history of Crohn's disease (CD; n = 3) were placed in explant culture and exposed to an adenoviral vector carrying the nuclear targeted beta-galactosidase reporter gene.


RESULTS
X-Gal staining showed that the total number of transduced cells per square millimeter was greater in UC explants than in controls (mean, 11.3 versus 0.9 blue nuclei/mm, respectively; P < 0.02) and that the frequency of epithelial cell transduction was greater in UC explants than in controls (86% versus 47% of explants, respectively; P = 0.01). Transduction of mature columnar surface epithelial cells occurred exclusively in UC and CD explants and was not seen in controls. Attenuated epithelial cells at sites of tissue damage or ulceration showed increased transduction compared with mature columnar epithelial cells (62% versus 19% of occurrences, respectively; P < 0.0001).


CONCLUSIONS
We conclude that intestinal epithelial cells from IBD patients are more readily transfected by standard adenoviral vectors than are those from control patients. These results suggest that targeting genes to inflamed intestine through the luminal route may be possible.
Schmiedlin-Ren
Phyllissa
P
University of Michigan Medical School, Ann Arbor, 48109, USA.
Kesisoglou
Filippos
F
Mapili
John A
JA
Sabek
Sayed E
SE
Barnett
Jeffrey L
JL
Chey
William D
WD
Roessler
Blake
B
Zimmermann
Ellen M
EM
D000256:Adenoviridae; D000328:Adult; D003093:Colitis, Ulcerative / Q000473:pathology*; D003106:Colon / Q000473:pathology*; D003424:Crohn Disease / Q000473:pathology*; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D008297:Male; D008875:Middle Aged; D046509:Tissue Culture Techniques; D014161:Transduction, Genetic; D001616:beta-Galactosidase / Q000235:genetics*
D001616:beta-Galactosidase