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Intestinal Preservation Injury: A Comparison Between Rat, Porcine and Human Intestines

Journal article
Authors John M. Söfteland
Anna Casselbrant
A. R. Biglarnia
J. Linders
Mats Hellström
A. Pesce
Arvind M. Padma
L. P. Jiga
B. Hoinoiu
M. Ionac
Mihai Oltean
Published in International Journal of Molecular Sciences
Volume 20
Issue 13
ISSN 1422-0067
Publication year 2019
Published at Institute of Clinical Sciences, Department of Surgery
Institute of Clinical Sciences, Department of Gastrosurgical Research and Education
Language en
Links dx.doi.org/10.3390/ijms20133135
Keywords tight junctions, organ preservation, intestine, transplantation, ischemia, intestinal mucosa, small-bowel transplantation, reperfusion injury, ischemia, barrier, cell, dysfunction, expression, apoptosis, donors, Biochemistry & Molecular Biology, Chemistry
Subject categories Clinical Medicine

Abstract

Advanced preservation injury (PI) after intestinal transplantation has deleterious short- and long-term effects and constitutes a major research topic. Logistics and costs favor rodent studies, whereas clinical translation mandates studies in larger animals or using human material. Despite diverging reports, no direct comparison between the development of intestinal PI in rats, pigs, and humans is available. We compared the development of PI in rat, porcine, and human intestines. Intestinal procurement and cold storage (CS) using histidine-tryptophan-ketoglutarate solution was performed in rats, pigs, and humans. Tissue samples were obtained after 8, 14, and 24 h of CS), and PI was assessed morphologically and at the molecular level (cleaved caspase-3, zonula occludens, claudin-3 and 4, tricellulin, occludin, cytokeratin-8) using immunohistochemistry and Western blot. Intestinal PI developed slower in pigs compared to rats and humans. Tissue injury and apoptosis were significantly higher in rats. Tight junction proteins showed quantitative and qualitative changes differing between species. Significant interspecies differences exist between rats, pigs, and humans regarding intestinal PI progression at tissue and molecular levels. These differences should be taken into account both with regards to study design and the interpretation of findings when relating them to the clinical setting.

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