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Commentaries

Strategies to Improve the Oxygen Supply to Microencapsulated Islets

Brandhorst, Daniel PhD1; Brandhorst, Heide PhD1; Johnson, Paul R. V. MD1

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doi: 10.1097/TP.0000000000002897
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Strategies for islet encapsulation have progressed exponentially during the past decade. Innovative and biocompatible materials have been engineered for optimized islet immunoisolation as successfully demonstrated in small and large animal models.1 Nevertheless, the inadequate oxygen supply to encapsulated tissue prevents the long-term survival and function of transplanted islets when implanted in highly efficient immunoprotective devices as previously described.2 Unless the delivery of oxygen to encapsulated cells is not substantially improved, local graft hypoxia represents the major limitation to the translation of islet encapsulation into the clinical setting.

Although different mathematical models have suggested that the oxygen supply using macroencapsulation devices is inferior compared with microencapsulation techniques, the latter still requires substantial improvement in terms of oxygenation of the encapsulated cells.3,4 In their article, Safley et al5 present an interesting attempt to optimize oxygenation of microcapsules by implementing oxygen carriers into the encapsulation material. This group used an experimental model, which was first applied to different graft sites in rats,6 to measure the local oxygen levels in nonhuman primates using a noninvasive technique. Although a continuous decrease of the local PO2 was noted in the peritoneal cavity during an observation period of 7 days, this approach enabled oxygen levels in or around the cell-free capsules that are higher as the PO2 measured in the peritoneal cavity of different species.1

To bring this concept closer to clinical application, experiments in nonhuman primates transplanted with islet-loaded microcapsules are essential in the near future to provide a proof of concept. In this context, previous observations, indicating that perfluorochemical-based oxygen carriers seem to have a detrimental effect on the viability of encapsulated islets, have to be carefully considered.7 In order to manufacture alginate composites with a superior biocompatibility and minimal proinflammatory potency, innovative materials with oxygen-delivering properties, such as the hemoglobin-related pigment from marine invertebrates, should be implemented in comparative studies.8

REFERENCES

1. Papas KK, De Leon H, Suszynski TM, et al. Oxygenation strategies for encapsulated islet and beta cell transplants.Adv Drug Deliv Rev2019139139–156
2. Safley SA, Kenyon NS, Berman DM, et al. Microencapsulated adult porcine islets transplanted intraperitoneally in streptozotocin-diabetic non-human primates.Xenotransplantation201825e12450
3. Iwata H, Arima Y, Tsutsui Y. Design of bioartificial pancreases from the standpoint of oxygen supply.Artif Organs201842E168–E185
4. Cao R, Avgoustiniatos E, Papas K, et al. Mathematical predictions of oxygen availability in micro- and macro-encapsulated human and porcine pancreatic islets.J Biomed Mater Res B Appl Biomater20201082343–352
5. Safley SA, Graham ML, Weegman BP, et al. Noninvasive fluorine-19 magnetic resonance relaxometry measurement of the partial pressure of oxygen in acellular perfluorochemical-loaded alginate microcapsules implanted in the peritoneal cavity of nonhuman primates.Transplantation2020104259–269
6. Nöth U, Gröhn P, Jork A, et al. 19F-MRI in vivo determination of the partial oxygen pressure in perfluorocarbon-loaded alginate capsules implanted into the peritoneal cavity and different tissues.Magn Reson Med1999421039–1047
7. Johnson AS, O’Sullivan E, D’Aoust LN, et al. Quantitative assessment of islets of langerhans encapsulated in alginate.Tissue Eng Part C Methods201117435–449
8. Rodriguez-Brotons A, Bietiger W, Peronet C, et al. Comparison of perfluorodecalin and hemoxcell as oxygen carriers for islet oxygenation in an in vitro model of encapsulation.Tissue Eng Part A2016221327–1336
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