Human Islet Viability and Function Is Maintained During High-density Shipment in Silicone Rubber Membrane Vessels

The shipment of human islets from processing centers to distant laboratories is beneficial for both research and clinical applications. The maintenance of islet viability and function in transit is critically important. Gas-permeable silicone rubber membrane (SRM) vessels reduce the risk of hypoxia-induced death or dysfunction during high-density islet culture or shipment. SRM vessels may offer additional advantages: they are cost-effective (fewer flasks, less labor needed), safer (lower contamination risk), and simpler (culture vessel can also be used for shipment). Human islets(IE) were isolated from two manufacturing centers and shipped in 10cm(2) surface area SRM vessels in temperature and pressure controlled containers to a distant center following at least two days of culture (n = 6). Three conditions were examined: low density (LD), high density (HD), and a micro centrifuge tube negative control (NC). LD was designed to mimic the standard culture density for human islet preparations (200 IE/cm(2)), while HD was designed to have a 20-fold higher tissue density, which would enable the culture of an entire human isolation in 1–3 vessels. Upon receipt, islets were assessed for viability, measured by oxygen consumption rate normalized to DNA content (OCR/DNA), and quantity, measured by DNA, and, when possible, potency and function with dynamic glucose-stimulated insulin secretion (GSIS) measurements and transplants in immunodeficient B6 rag mice. Post-shipment OCR/DNA was not reduced in HD versus LD, and was substantially reduced in the NC condition. HD islets exhibited normal function post-shipment. Based on the data we conclude that entire islet isolations (up to 400,000 IE) may be shipped using a single, larger SRM vessel with no negative effect on viability and ex vivo and in vivo function

A predictive computational platform for optimizing the design of bioartificial pancreas devices

The delivery of encapsulated islets or stem cell-derived insulin-producing cells (i.e., bioartificial pancreas devices) may achieve a functional cure for type 1 diabetes, but their efficacy is limited by mass transport constraints. Modeling such constraints is thus desirable, but previous efforts invoke simplifications which limit the utility of their insights. Herein, we present a computational platform for investigating the therapeutic capacity of generic and user-programmable bioartificial pancreas devices, which accounts for highly influential stochastic properties including the size distribution and random localization of the cells. We first apply the platform in a study which finds that endogenous islet size distribution variance significantly influences device potency. Then we pursue optimizations, determining ideal device structures and estimates of the curative cell dose. Finally, we propose a new, device-specific islet equivalence conversion table, and develop a surrogate machine learning model, hosted on a web application, to rapidly produce these coefficients for user-defined devices. © 2022, The Author(s).Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Walking mediates associations between neighborhood activity supportiveness and BMI in the Women's Health Initiative San Diego cohort

OBJECTIVES: To investigate whether walking mediates neighborhood built environment associations with weight status in middle- and older-aged women. METHODS: Participants (N=5085; mean age=64±7.7; 75.4% White non-Hispanic) were from the Women’s Health Initiative San Diego cohort baseline visits. Body mass index (BMI) and waist circumference were measured objectively. Walking was assessed via survey. The geographic information system (GIS)-based home neighborhood activity supportiveness index included residential density, street connectivity, land use mix, and number of parks. RESULTS: BMI was 0.22 units higher and the odds ratio for being obese (vs. normal or overweight) was 8% higher for every standard deviation decrease in neighborhood activity supportiveness. Walking partially mediated these associations (22–23% attenuation). Findings were less robust for waist circumference. CONCLUSIONS: Findings suggest women who lived in activity-supportive neighborhoods had a lower BMI than their counterparts, in part because they walked more. Improving neighborhood activity supportiveness has population-level implications for improving weight status and health