Optimal Time to Ship Human Islets Post Tissue Culture to Maximize Islet

Abstract

Access to functional high-quality pancreatic human islets is critical to advance diabetes research. The Integrated Islet Distribution Program (IIDP), a major source for human islet distribution for over 15 years, conducted a study to evaluate the most advantageous times to ship islets postisolation to maximize islet recovery. For the evaluation, three experienced IIDP Islet Isolation Centers each provided samples from five human islet isolations, shipping 10,000 islet equivalents (IEQ) at four different time periods postislet isolation (no 37°C culture and shipped within 0 to 18 hours; or held in 37°C culture for 18 to 42, 48 to 96, or 144 to 192 hours). A central evaluation center compared samples for islet quantity, quality, and viability for each experimental condition preshipment and postshipment, as well as post 37°C culture 18 to 24 hours after shipment receipt. Additional evaluations included measures of functional potency by static glucose-stimulated insulin release (GSIR), represented as a stimulation index. Comparing the results of the four preshipment holding periods, the greatest IEQ loss postshipment occurred with the shortest preshipment times. Similar patterns emerged when comparing preshipment to postculture losses. In vitro islet function (GSIR) was not adversely impacted by increased tissue culture time. These data indicate that allowing time for islet recovery postisolation, prior to shipping, yields less islet loss during shipment without decreasing islet function.

Keywords: culture; diabetes; human islets; shipping times.

Figure 1.

Change in islet equivalent (IEQ) count from preshipment to postshipment by preshipment culture time periods. This figure shows that the change between preshipment and postshipment counts stabilizes as the preshipment culture time expands, with the least IEQ loss at the 144 to 196 hours preshipment culture time. The boxplots depict the mean with a diamond; the median is represented by the line within the box; 25th and 75th percentiles by the lower and upper bounds of a box. The distance between 25th and 75th percentile – interquartile range (IQR). Whiskers end at the last data point before 1.5 × IQR below 25th percentile or above 75th percentile. Hollow circles depict outliers of the specific distribution. P-values are noted for the statistically significant changes in IEQ count between preshipment culture time periods 0 to 18 and 144 to 192 hours (P =0 .001) and between 18 to 42 and 144 to 192 hours (P = 0.036).