TY - JOUR
T1 - Intestinal preservation injury
T2 - A comparison between rat, porcine and human intestines
AU - Søfteland, John Mackay
AU - Casselbrant, Anna
AU - Biglarnia, Ali Reza
AU - Linders, Johan
AU - Hellström, Mats
AU - Pesce, Antonio
AU - Padma, Arvind Manikantan
AU - Jiga, Lucian Petru
AU - Hoinoiu, Bogdan
AU - Ionac, Mihai
AU - Oltean, Mihai
PY - 2019/7/1
Y1 - 2019/7/1
N2 - 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.
AB - 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.
KW - Intestinal mucosa
KW - Intestine
KW - Ischemia
KW - Organ preservation
KW - Tight junctions
KW - Transplantation
UR - http://www.scopus.com/inward/record.url?scp=85068593122&partnerID=8YFLogxK
U2 - 10.3390/ijms20133135
DO - 10.3390/ijms20133135
M3 - Article
C2 - 31252560
AN - SCOPUS:85068593122
SN - 1661-6596
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 13
M1 - 3135
ER -