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Lookup NU author(s): Dr Bill ScottORCiD
This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).
Introduction: Conventional culture conditions, such as in T-flasks, require thatoxygen diffuse through the medium to reach the islets; in turn, islet surface areadensity is limited by oxygen availability. To culture a typical clinical isletpreparation may require more than 20 T-175 flasks at the standard surfacearea density of 200 IE/cm2. To circumvent this logistical constraint, we testedislets cultured on top of silicon gas-permeable (GP) membranes which placeislets in close proximity to ambient oxygen.Methods: Oxygenation of individual islets under three culture conditions,standard low-density, non-GP high density, and GP high density, were firstmodeled with finite element simulations. Porcine islets from 30 preparationswere cultured for 2 days in devices with GP membrane bottoms or in pairedcultures under conventional conditions. Islets were seeded at high density (HD,~4000 IE/cm2, as measured by DNA) in both GP and non-GP devices.Results: In simulations, individual islets under standard culture conditions andhigh density cultures on GP membranes were both well oxygenated whereasnon-GP high density cultured islets were anoxic. Similarly, compared to the non-GP paired controls, islet viability and recovery were significantly increased in HDGP cultures. The diabetes reversal rate in nude diabetic mice was similar for HDGP devices and standard cultures but was minimal with non-GP HD cultures.Discussion: Culturing islets in GP devices allows for a 20-fold increase of isletsurface area density, greatly simplifying the culture process while maintaining isletviability and metabolism.
Author(s): Avgoustiniatos ES, Mueller KR, Scott III WE, Kitzmann JP, Suszynski TM, Perrault BE, Falde EJ, Balamurugan AN, Hering BJ, Putnam CW, Papas KK
Publication type: Article
Publication status: Published
Journal: Frontiers in Bioengineering and Biotechnology
Year: 2024
Volume: 12
Online publication date: 11/07/2024
Acceptance date: 21/06/2024
Date deposited: 18/11/2025
ISSN (electronic): 2296-4185
Publisher: Frontiers Media SA
URL: https://doi.org/10.3389/fbioe.2024.1401608
DOI: 10.3389/fbioe.2024.1401608
Data Access Statement: The original contributions presented in the study are included in the article/Supplementary Material, further inquiries can be directed to the corresponding author.
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