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Open Access Hypothermic Perfusion Preservation of Pancreas for Islet Grafts: Validation Using a Split Lobe Porcine Model

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Abstract:

The demand for high-quality islets for transplantation in type I diabetics will increase as the current clinical trials transition into standard of care. The mode of preservation of donor pancreata is critical to this mission since islets are very sensitive to ischemic injury. Hypothermic perfusion preservation (HPP) is being investigated for extended pancreas preservation in light of the beneficial effects reported for other organs. The present pilot study aimed to establish the potency of porcine islets isolated from pancreata after 24 h of HPP at 4‐8°C. The study design included a split-lobe pancreas model that permitted paired comparisons of islets isolated from 24-h HPP splenic lobes with nonperfused, fresh control duodenal/connecting lobes stored at 4°C for <3 h. Prior to transplantation, islet viability was assessed in vitro using the ratio of oxygen consumption rate to DNA (OCR/DNA) assay and correlated with subsequent in vivo function by transplantation in diabetic immunodeficient mice. The OCR/DNA (mean ± SD) measured after 7 days of culture and immediately prior to transplantation for islets from the 24-h HPP group was 269 ± 19 nmol/min/mg DNA, which was higher but not statistically different to the mean of 236 ± 43 for the counterpart control group. All four nude mice transplanted with islets from the 24-h HPP group showed diabetes reversal, compared with five of six transplants from the control group. In conclusion, islets isolated from adult porcine pancreata after 24-h HPP exhibited high viability as measured by OCR/DNA and were able to consistently reverse diabetes in a nude mouse bioassay.

Keywords: Hypothermic perfusion; Islet; Oxygen consumption; Pancreas; Perfusion; Viability

Document Type: Research Article

DOI: https://doi.org/10.3727/215517911X617897

Publication date: 2012-01-01

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  • The importance of translating original, peer-reviewed research and review articles on the subject of cell therapy and its application to human diseases to society has led to the formation of the journal Cell Medicine. To ensure high-quality contributions from all areas of transplantation, the same rigorous peer review will be applied to articles published in Cell Medicine. Articles may deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, and stem cells, among others. Basic clinical studies and immunological research papers may also be featured if they have a translational interest. To provide complete coverage of this revolutionary field, Cell Medicine will report on relevant technological advances and their potential for translational medicine. Cell Medicine will be a purely online Open Access journal. There will therefore be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow your work to be disseminated to a wider audience and also entitle you to a free PDF, as well as prepublication of an unedited version of your manuscript.
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