Abstract
Background. We have utilized a noninvasive technique for measuring the partial pressure of oxygen (pO2) in alginate microcapsules implanted intraperitoneally in healthy nonhuman primates (NHPs). Average pO2 is important for determining if a transplant site and capsules with certain passive diffusion characteristics can support the islet viability, metabolic activity, and dose necessary to reverse diabetes. Methods. Perfluoro-15-crown-5-ether alginate capsules were infused intraperitoneally into 3 healthy NHPs. Peritoneal pO2 levels were measured on days 0 and 7 using fluorine-19 magnetic resonance relaxometry and a fiber-optic probe. Fluorine-19 MRI was used to determine the locations of capsules within the peritoneal space on days 0 and 7. Gross and histologic evaluations of the capsules were used to assess their biocompatibility postmortem. Results. At day 0 immediately after infusion of capsules equilibrated to room air, capsules were concentrated near the infusion site, and the pO2 measurement using magnetic resonance relaxometry was 147 ± 9 mm Hg. On day 7 after capsules were dispersed throughout the peritoneal cavity, the pO2 level was 61 ± 11 mm Hg. Measurements using the fiber-optic oxygen sensor were 132 ± 7.5 mm Hg (day 0) and 89 ± 6.1 mm Hg (day 7). Perfluoro-15-crown-5-ether capsules retrieved on day 7 were intact and free-floating without host cell attachment, although the numbers of peritoneal CD20+ B cells, CD4+ and CD8+ T cells, and CD14+ macrophages increased consistent with a mild foreign body reaction. Conclusions. The peritoneal pO2 of normal NHPs is relatively low and we predict would decrease further when encapsulated islets are transplanted intraperitoneally.
Original language | English (US) |
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Pages (from-to) | 259-269 |
Number of pages | 11 |
Journal | Transplantation |
Volume | 104 |
Issue number | 2 |
DOIs | |
State | Published - Feb 1 2020 |
Bibliographical note
Funding Information:This study was supported by a grant from the Juvenile Diabetes Research Foundation (Strategic Research Agreement), the National Institutes of Health (P41 EB015894 and S10 RR023730), the Minnesota Lions Diabetes Foundation, the Schott Family Foundation, the Carol Olson Memorial Diabetes Research Fund, and by generous gifts from Malcolm and Musette Powell and from Maxine Clippert.
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