Luminal polyethylene glycol solution delays the onset of preservation injury in the human intestine.

The organ damage incurred during the cold storage (CS) of intestinal grafts has short and long-term consequences. Animal studies suggest that additional luminal preservation (LP) with polyethylene glycol (PEG) may alleviate this damage. This study aims to validate these findings using human intestines. Ileal segments, perfused intravascularly with IGL-1 solution, were procured from 32 multiorgan donors and divided into two parts: one containing a PEG 3350-based solution introduced luminally (LP group) and another one without luminal treatment (control). Sampling was performed after 4 h, 8 h, 14 h, and 24 h of CS. Histology was assessed using the Chiu/Park score. Tight junctions (TJ), several inflammatory markers, and transcription factors were examined by immunofluorescence, ddPCR, and western blot. Tissue water content (edema) was also measured. Apoptotic activity was assessed with caspase -2, -3, and -9 assays. LP significantly lowered mucosal injury at all time points. Redistribution of TJ proteins occurred earlier and more severely in the control group. After 24 h of CS, LP intestines showed an emerging unfolding protein response. Increased caspase-3 and -9 activity was found in the control group. The current results indicate that luminal PEG is safe and effective in reducing damage to the intestinal epithelium during CS. © 2020 The American Society of Transplantation and the American Society of Transplant Surgeons.

Citation

John M Søfteland, Jasmine Bagge, Arvind M Padma, Anna Casselbrant, Changlian Zhu, Yafeng Wang, Mats Hellström, Michael Olausson, Mihai Oltean. Luminal polyethylene glycol solution delays the onset of preservation injury in the human intestine. American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons. 2021 Jun;21(6):2220-2230

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PMID: 33249756

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