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

Transplantation. 2020 Feb;104(2):259-269. doi: 10.1097/TP.0000000000002896.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alginates / pharmacology*
  • Animals
  • Capsules
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / surgery*
  • Female
  • Fluorine-19 Magnetic Resonance Imaging / methods*
  • Graft Survival
  • Islets of Langerhans Transplantation / methods*
  • Macaca mulatta
  • Oxygen / metabolism*
  • Oxygen Consumption / physiology*
  • Partial Pressure
  • Peritoneal Cavity / surgery*

Substances

  • Alginates
  • Capsules
  • Oxygen