Abstract
Preservation of cell quality during shipment of human pancreatic islets for use in laboratory research is a crucial, but neglected, topic. Mammalian cells, including islets, have been shown to be adversely affected by temperature changes in vitro and in vivo, yet protocols that control for thermal fluctuations during cell transport are lacking. To evaluate an optimal method of shipping human islets, an initial assessment of transportation conditions was conducted using standardized materials and operating procedures in 48 shipments sent to a central location by eight pancreas-processing laboratories using a single commercial airline transporter. Optimization of preliminary conditions was conducted, and human islet quality was then evaluated in 2,338 shipments pre- and postimplementation of a finalized transportation container and standard operating procedures. The initial assessment revealed that the outside temperature ranged from a mean of -4.6 ± 10.3°C to 20.9 ± 4.8°C. Within-container temperature drops to or below 15°C occurred in 16 shipments (36%), while the temperature was found to be stabilized between 15°C and 29°C in 29 shipments (64%). Implementation of an optimized transportation container and operating procedure reduced the number of within-container temperature drops (≤ 15°C) to 13% (n = 37 of 289 winter shipments), improved the number desirably maintained between 15°C and 29°C to 86% (n = 250), but also increased the number reaching or exceeding 29°C to 1% (n = 2; overall p < 0.0001). Additionally, postreceipt quality ratings of excellent to good improved pre- versus postimplantation of the standardized protocol, adjusting for preshipment purity/viability levels (p < 0.0001). Our results show that extreme temperature fluctuations during transport of human islets, occurring when using a commercial airline transporter for long distance shipping, can be controlled using standardized containers, materials, and operating procedures. This cost-effective and pragmatic standardized protocol for the transportation of human islets can potentially be adapted for use with other mammalian cell systems and is available online at http://iidp.coh.org/sops.aspx.
Highlights
Human pancreatic islets play a vital role in laboratory research and are being used in islet transplantation for a subset of individuals with type 1 diabetes [22]
Because human islet isolation is expensive [12] and requires specialized facilities staffed with experienced personnel, the need for islet shipping protocols to extend the services of established pancreas processing centers to distant clinical transplant centers and basic science laboratories is growing [10]
Detailed information on temperature and transportation of standardized islet shipping containers was collected for this study. a Total of nine participating sites, that is, eight laboratories and one coordinating center. b Number of shipments. c Other variables collected included departure/ arrival times and cities and total miles traveled. d Departing, arriving, and all hub stop city temperatures collected using data provided by www.weather.com
Summary
Human pancreatic islets play a vital role in laboratory research and are being used in islet transplantation for a subset of individuals with type 1 diabetes [22]. A number of published articles have reviewed the cold [1] and heat [40] shock responses of mammalian cells, including studies on gene expression changes during periods of thermal fluctuation [50,51]. Such reports suggest a need to account for thermal effects on cell biology experiments, including any undesirable temperature changes during transportation of human islets. Unlike tumor-derived or artificially immortalized cell lines [16], primary human pancreatic islets have a finite lifespan and cannot be readily stored or cultured for long periods of time, certain exceptions exist [26,44]
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