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Title: The size of endothelial fenestrae in human liver sinusoids: implications for hepatocyte-directed gene transfer
Authors: Wisse, E *
Jacobs, Frank *
Topal, Baki
Frederik, P
De Geest, Bart # ×
Issue Date: Sep-2008
Publisher: Macmillan Press Ltd.
Series Title: Gene Therapy vol:15 issue:17 pages:1193-1199
Abstract: Fenestrae allow the passage of gene transfer vectors from the sinusoidal lumen to the surface of hepatocytes. We have previously shown that the diameter of fenestrae correlates with species and strain differences of transgene expression following intravenous adenoviral transfer. In the current study, we demonstrate that the diameter of fenestrae in humans without liver pathology is 107+/-1.5 nm. This is similar to the previously reported diameter in New Zealand White (NZW) rabbits (103+/-1.3 nm) and is significantly smaller than in C57BL/6 mice (141+/-5.4 nm) and Sprague-Dawley rats (161+/-2.7 nm). We show that the diameter of fenestrae in one male NZW rabbit and its offspring characterized by a more than 50-fold increase of transgene expression after adenoviral gene transfer is significantly (113+/-1.5 nm; P<0.001) larger than in control NZW rabbits. In vitro filtration experiments using polycarbonate filters with increasing pore sizes demonstrate that a relatively small increment of the diameter of pores potently enhances passage of adenoviral vectors, consistent with in vivo data. In conclusion, the small diameter of fenestrae in humans is likely to be a major obstacle for hepatocyte transduction by adenoviral vectors.
URI: 
ISSN: 0969-7128
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Abdominal Surgical Oncology
Molecular and Vascular Biology
* (joint) first author
× corresponding author
# (joint) last author

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