Susan A Safley1, Melanie L Graham2, Bradley P Weegman3,4, Samuel A Einstein4,5, Graham F Barber1, Jody J Janecek2, Lucas A Mutch2, Amar Singh6, Sabarinathan Ramachandran7, Michael Garwood4, Athanassios Sambanis6, Klearchos K Papas8, Bernhard J Hering7, Collin J Weber1. 1. Department of Surgery, Emory University, Atlanta, GA. 2. Preclinical Research Center, Department of Surgery, University of Minnesota, St. Paul, MN. 3. Sylvatica Biotech, Inc., Charleston, SC. 4. Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, MN. 5. Department of Imaging Physics, The University of Texas MD Anderson Cancer Center, Houston, TX. 6. Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, MN. 7. Department of Surgery, University of Arizona, Tucson, AZ. 8. W. M. Keck Foundation, Medical Research Division, Los Angeles, CA.
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.
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.
Authors: R B Elliott; L Escobar; P L J Tan; O Garkavenko; R Calafiore; P Basta; A V Vasconcellos; D F Emerich; C Thanos; C Bambra Journal: Transplant Proc Date: 2005-10 Impact factor: 1.066
Authors: Samuel A Einstein; Bradley P Weegman; Meri T Firpo; Klearchos K Papas; Michael Garwood Journal: Tissue Eng Part C Methods Date: 2016-11 Impact factor: 3.056
Authors: Nassir Rostambeigi; Ian R Lanza; Petras P Dzeja; Michael C Deeds; Brian A Irving; Honey V Reddi; Pranathi Madde; Song Zhang; Yan W Asmann; Jarett M Anderson; Jill M Schimke; K Sreekumaran Nair; Norman L Eberhardt; Yogish C Kudva Journal: Transplantation Date: 2011-03-27 Impact factor: 4.939
Authors: Siyuan Liu; Sameer J Shah; Lisa J Wilmes; John Feiner; Vikram D Kodibagkar; Michael F Wendland; Ralph P Mason; Nola Hylton; Harriet W Hopf; Mark D Rollins Journal: Magn Reson Med Date: 2011-06-17 Impact factor: 4.668