Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.

Pancreas transportation between donor center and islet production facility is frequently associated with prolonged ischemia impairing islet isolation and transplantation outcomes. It is foreseeable that shipment of pig pancreases from distant centralized biosecure breeding facilities to institutes t...

Ful tanımlama

Detaylı Bibliyografya
Asıl Yazarlar: Brandhorst, H, Iken, M, Scott, W, Papas, K, Theisinger, B, Johnson, P, Korsgren, O, Brandhorst, D
Materyal Türü: Journal article
Dil:English
Baskı/Yayın Bilgisi: 2013
_version_ 1826260719341928448
author Brandhorst, H
Iken, M
Scott, W
Papas, K
Theisinger, B
Johnson, P
Korsgren, O
Brandhorst, D
author_facet Brandhorst, H
Iken, M
Scott, W
Papas, K
Theisinger, B
Johnson, P
Korsgren, O
Brandhorst, D
author_sort Brandhorst, H
collection OXFORD
description Pancreas transportation between donor center and islet production facility is frequently associated with prolonged ischemia impairing islet isolation and transplantation outcomes. It is foreseeable that shipment of pig pancreases from distant centralized biosecure breeding facilities to institutes that have a long-term experience in porcine islet isolation is essentially required in future clinical islet xenotransplantation. Previously, we demonstrated that perfluorohexyloctan (F6H8) is significantly more efficient to protect rat and human pancreata from ischemically induced damage compared to perfluorodecalin (PFD). To evaluate the effect of F6H8 on long-term stored pig pancreases in a prospective study, we utilized the split lobe model to minimize donor variability. Retrieved pancreases were dissected into the connecting and splenic lobe, intraductally flushed with UW solution and immersed alternately in either preoxygenated F6H8 or PFD for 8-10 h. Prior to pancreas digestion, the intrapancreatic pO2 and the ratio of ATP-to-inorganic phosphate was compared utilizing 31P-NMR spectroscopy. Isolated islets were cultured for 2-3 days at 37°C and subjected to quality assessment. Pancreatic lobes stored in preoxygenated F6H8 had a significantly higher intrapancreatic pO2 compared to pancreata in oxygen-precharged PFD (10.11 ± 3.87 vs. 1.64 ± 1.13 mmHg, p < 0.05). This correlated with a higher ATP-to-inorganic phosphate ratio (0.30 ± 0.04 vs. 0.14 ± 0.01). No effect was observed concerning yield and purity of freshly isolated islets. Nevertheless, a significantly improved glucose-stimulated insulin response, increased viability and postculture survival (57.2 ± 5.7 vs. 39.3 ± 6.4%, p < 0.01) was measured in islets isolated from F6H8-preserved pancreata. The present data suggest that F6H8 does not increase islet yield but improves quality of pig islets isolated after prolonged cold ischemia.
first_indexed 2024-03-06T19:10:09Z
format Journal article
id oxford-uuid:167ba910-3f2a-4e94-8edb-1eee42dd802d
institution University of Oxford
language English
last_indexed 2024-03-06T19:10:09Z
publishDate 2013
record_format dspace
spelling oxford-uuid:167ba910-3f2a-4e94-8edb-1eee42dd802d2022-03-26T10:31:41ZQuality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:167ba910-3f2a-4e94-8edb-1eee42dd802dEnglishSymplectic Elements at Oxford2013Brandhorst, HIken, MScott, WPapas, KTheisinger, BJohnson, PKorsgren, OBrandhorst, DPancreas transportation between donor center and islet production facility is frequently associated with prolonged ischemia impairing islet isolation and transplantation outcomes. It is foreseeable that shipment of pig pancreases from distant centralized biosecure breeding facilities to institutes that have a long-term experience in porcine islet isolation is essentially required in future clinical islet xenotransplantation. Previously, we demonstrated that perfluorohexyloctan (F6H8) is significantly more efficient to protect rat and human pancreata from ischemically induced damage compared to perfluorodecalin (PFD). To evaluate the effect of F6H8 on long-term stored pig pancreases in a prospective study, we utilized the split lobe model to minimize donor variability. Retrieved pancreases were dissected into the connecting and splenic lobe, intraductally flushed with UW solution and immersed alternately in either preoxygenated F6H8 or PFD for 8-10 h. Prior to pancreas digestion, the intrapancreatic pO2 and the ratio of ATP-to-inorganic phosphate was compared utilizing 31P-NMR spectroscopy. Isolated islets were cultured for 2-3 days at 37°C and subjected to quality assessment. Pancreatic lobes stored in preoxygenated F6H8 had a significantly higher intrapancreatic pO2 compared to pancreata in oxygen-precharged PFD (10.11 ± 3.87 vs. 1.64 ± 1.13 mmHg, p < 0.05). This correlated with a higher ATP-to-inorganic phosphate ratio (0.30 ± 0.04 vs. 0.14 ± 0.01). No effect was observed concerning yield and purity of freshly isolated islets. Nevertheless, a significantly improved glucose-stimulated insulin response, increased viability and postculture survival (57.2 ± 5.7 vs. 39.3 ± 6.4%, p < 0.01) was measured in islets isolated from F6H8-preserved pancreata. The present data suggest that F6H8 does not increase islet yield but improves quality of pig islets isolated after prolonged cold ischemia.
spellingShingle Brandhorst, H
Iken, M
Scott, W
Papas, K
Theisinger, B
Johnson, P
Korsgren, O
Brandhorst, D
Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.
title Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.
title_full Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.
title_fullStr Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.
title_full_unstemmed Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.
title_short Quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model.
title_sort quality of isolated pig islets is improved using perfluorohexyloctane for pancreas storage in a split lobe model
work_keys_str_mv AT brandhorsth qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT ikenm qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT scottw qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT papask qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT theisingerb qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT johnsonp qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT korsgreno qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel
AT brandhorstd qualityofisolatedpigisletsisimprovedusingperfluorohexyloctaneforpancreasstorageinasplitlobemodel