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

• Type of Material: Article
• Authors: Susan Safley, Emory University; Melanie L. Graham, University of Minnesota; Bradley P. Weegman, Sylvatica Biotech Inc; Samuel A. Einstein, University of Minnesota; Graham F. Barber, Emory University; Jody J. Janecek, University of Minnesota; Lucas A. Mutch, University of Minnesota; Amar Singh, University of Minnesota; Sabarinathan Ramachandran, University of Minnesota; Michael Garwood, University of Minnesota; Athanassios Sambanis, Emory University; Klearchos K. Papas, University of Arizona; Bernhard J. Hering, University of Minnesota; Collin Weber, Emory University
• Language: English
• Date: 2020-02-01
• Publisher: Lippincott Williams & Wilkins
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2019 Wolters Kluwer Health, Inc. All rights reserved.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1097/TP.0000000000002896
• Title of Journal or Parent Work: Transplantation
• Volume: 104
• Issue: 2
• Start Page: 259
• End Page: 269
• Grant/Funding Information: And by generous gifts from Malcolm and Musette Powell and from Maxine Clippert.; National Institutes of Health (P41 EB015894 and S10 RR023730),; This study was supported by a grant from the Juvenile Diabetes Research Foundation (Strategic Research Agreement),; Minnesota Lions Diabetes Foundation, the Schott Family Foundation, the Carol Olson Memorial Diabetes Research Fund,
• Keywords: Hypoxia; Pig islets; In-vitro; Science & Technology; Immunology; Life Sciences & Biomedicine; Transplantation; Rat; Reprograms; Dendritic cells; Dissolved oxygen; Porcine islets; Expression; Surgery
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Radiology; Health Sciences, Immunology

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.