High-resolution magic angle spinning nuclear magnetic resonance of donor pancreatic tissue may predict islet viability prior to isolation.

NMR Biomed

Surgical-Medical Research Institute, 1074 Dentistry/Pharmacy Centre, University of Alberta, Edmonton, Alberta, Canada.

Published: November 2024

AI Article Synopsis

  • Islet transplantation is a promising alternative to whole pancreas transplantation for type 1 diabetes patients facing severe hypoglycemia, but challenges remain regarding cost-effectiveness and donor sensitization.
  • This pilot study utilized advanced nuclear magnetic resonance spectroscopy to examine human pancreatic tissue before and after cold-storage, revealing signs of hypoxia and subsequent recovery of islet viability post-incubation.
  • A correlation was found between specific metabolic changes in the pancreatic tissue and the responsiveness of the isolated islets, indicating that assessing these features could help identify suitable pancreases and enhance transplantation outcomes.

Article Abstract

For patients with type 1 diabetes mellitus complicated by severe hypoglycemia, clinical islet transplantation is an efficacious alternative to whole pancreas transplantation. While islet transplantation has improved over the last few years, there remain questions regarding its cost-effectiveness and donor allosensitization, which is exacerbated when islets from more than one donor are required. Understanding the features of a pancreas that would provide viable islets prior to isolation may lead to development of an accurate assay that could identify suitable pancreases and provide significant cost savings to a clinical islet transplantation program. In this pilot study, solid-state high-resolution magic angle spinning (HRMAS) nuclear magnetic resonance (NMR) spectroscopy was used to assess samples of convenience of human pancreatic tissue taken prior to islet isolation both before and after incubation using the two-layer perfluorocarbon (PFC)/University of Wisconsin (UW) solution cold-storage method. We observed that, prior to incubation, human pancreatic tissue exhibited evidence of hypoxia with decreased peak integrals associated with glucose and increased peak integrals corresponding to lactate and free fatty acids. After incubation, we observed a reversal of the hypoxia-induced damage, as integrals corresponding to glucose increased, and those corresponding to lactate and free fatty acid resonances decreased. Interestingly, a significant correlation between the ratio of the glucose integral (at 3.0-4.5 ppm) to the sum of the fatty acid (at 0.9 ppm) and lactate + fatty acid (at 1.3 ppm) integrals and glucose responsiveness, a measure of islet viability, of the isolated islets, was observed after incubation in PFC/UW solution for pancreases that responded to PFC/UW solution incubation (p = 0.02). Notably, pancreases with little or no change in the integral ratio after PFC/UW solution incubation had poor recovery. These results suggest that tissue recovery is a key feature for determining islet cell viability, and further that HRMAS NMR may be a practical method to quickly assess human donor pancreatic tissue prior to islet isolation for clinical transplantation.

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http://dx.doi.org/10.1002/nbm.5207DOI Listing

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