Ischaemia impairs organ quality during preservation in a time-dependent manner, due to a lack of oxygen supply. Its impact on pancreas and islet transplantation outcome has been demonstrated by a correlation between cold ischaemia time and poor islet isolation efficiency. Our goal in the present study was to improve pancreas and islet quality using a novel natural oxygen carrier (M101, 2 g/L), which has been proven safe and efficient in other clinical applications, including kidney transplantation, and for several pre-clinical transplantation models. When M101 was added to the preservation solution of rat pancreas during ischaemia, a decrease in oxidative stress (ROS), necrosis (HMGB1), and cellular stress pathway (p38 MAPK)activity was observed. Freshly isolated islets had improved function when M101 was injected in the pancreas. Additionally, human pancreases exposed to M101 for 3 hours had an increase in complex 1 mitochondrial activity, as well as activation of AKT activity, a cell survival marker. Insulin secretion was also up-regulated for isolated islets. In summary, these results demonstrate a positive effect of the oxygen carrier M101 on rat and human pancreas during preservation, with an overall improvement in post-isolation islet quality.
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http://dx.doi.org/10.1111/jcmm.14666 | DOI Listing |
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National Institute of Science and Technology on Plant Physiology under Stress Conditions, Departamento de Biologia Vegetal, Universidade Federal de Viçosa, Viçosa 36570-900, Minas Gerais, Brazil.
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Department of Pharmacy, University of Pisa, Via Bonanno, 6, 56126 Pisa, Italy.
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Hainan Engineering Research Center of Tropical Ocean Advanced Optoelectronic Functional Materials, Hainan International Joint Research Center of Marine Advanced Photoelectric Functional Materials, Key Laboratory of Laser Technology and Optoelectronic Functional Materials of Hainan Province, Key Laboratory of Functional Materials and Photoelectrochemistry of Haikou, College of Chemistry and Chemical Engineering, Hainan Normal University, Haikou 571158, China.
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Department of Chemistry and Waterloo Institute for Nanotechnology, University of Waterloo, Waterloo, ON N2L 3G1, Canada.
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