1144-P: Chemical Assessment of Populations of Human Pancreatic Islets Isolated for Transplantation

Abstract

Clinical transplantation of human cadaveric islets is an important therapy for the treatment of T1D. Such transplantation has demonstrated safety and efficacy in academic and clinical trials. Quality control during all stages of islet isolation, handling, and transplantation is critical for success of the therapy. A variety of tests are used to assess cellular integrity, islet population purity, and potency. Unfortunately, most of applied tests are not evaluating individual pancreatic islet chemical compositions which are indicative of overall islets functional and health state. Here we describe the results of mass spectrometric (MS) assessment of populations of individual pancreatic islets received from seven donors including four T2D cases. Random sampling and MS analysis of 232 islet-like structures detected 150 islets (based on size, morphology, and visual inspection). Our findings correlate (R2=0.9) with data on sample purity for different batches provided by the ADI IsletCore. The classic pancreatic islet hormones are observed in the majority of islets. Peptide profiles are mostly dominated by insulin, although we observe a greater variability of insulin peaks than somatostatin- and glucagon-related signals by mass spectrometry. No significant differences in our results are observed between healthy and T2D-affected islets. Fast mass-spectrometry-based assessment allowed selection of representative individual islets for liquid chromatography-MS (LC-MS), which provides an in-depth chemical coverage. Using LC-MS, a number of histone-related peptides are detected significantly expanding analyte coverage. To increase the throughput of direct MS analysis of islets, we use our optically guided mass spectrometry approach to automate the localization and analysis of larger islet populations. Using this technology and MS detection, hundreds of islets can be profiled for presence of a variety of metabolites, lipids, and peptides during a several-hour timespan. Disclosure S. Rubakhin: None. E. V. Romanova: None. J. V. Sweedler: None. Funding American Diabetes Association/Pathway to Stop Diabetes (1-18-VSN-19 to J.V.S.)