About this item:

45 Views | 27 Downloads

Author Notes:

Correspondence: Susan A. Safley, PhD, Department of Surgery, Emory University, 1365 Clifton Road, NE, Building A, Atlanta GA 30322, ssafley@emory.edu

Author contributions: S.A.S. and M.L.G. are co-first authors; S.A.S. directed the PFCE encapsulation; M.L.G. directed all aspects of the NHP experiments, performed implant, biopsy, gross pathology, and associated data analysis;

B.L.W. constructed the surface coil used in experiments, generated the calibration curve, performed MRI imaging of NHPs, analyzed the MRI data, and co-drafted the article; S.A.E. advised on MRI imaging, analyzed the MRI data, and co-drafted the article;

G.F.B. generated the PFCE capsules for all experiments and contributed to the manuscript; J.J.J and L.A.M provided expert animal care, carried out experiments, and collected data, AS and SR developed the flow cytometry panels used in this study and acquired and analyzed the phenotyping data presented in this manuscript,

M.G. designed the 19F MRI experiments, reviewed and analyzed data; A.S. contributed to the design of the PFCE capsules, consulted on oxygen measurement and contributed to drafting the manuscript; K.K.P. assisted in designing the 19F MRI experiments and served as consultant on oxygen measurement;

B.J.H. directed the flow cytometric analysis and microscopic evaluation of capsules, contributed to overall experimental design, and reviewed the manuscript; C.J.W. provided expertise in encapsulation and reviewed the manuscript.

All authors read the journal’s authorship agreement, and all authors read and approved the final version of the article.

Acknowledgements: We gratefully acknowledge the entire caregiver team at the University of Minnesota’s Preclinical Research Center performing NHP studies; as well as Johannes Leisen, Ph.D., Assistant Director of the Georgia Institute of Technology NMR Service Center, Atlanta, GA, who performed the 19F scans and quality control assessment of the PFCE capsules prepared at Emory.

We would like to thank Momin Siddiqui, M.D., Departments of Pathology at Emory University and Weill Cornell Medical College for careful analysis of host cells on explanted PFCE capsules in H&E-stained slides.

Disclosures: The authors declare no conflicts of interest.

Subjects:

Research Funding:

This study was supported by a grant from the Juvenile Diabetes Research Foundation (Strategic Research Agreement),

National Institutes of Health (P41 EB015894 and S10 RR023730),

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.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Immunology
  • Surgery
  • Transplantation
  • Dissolved oxygen
  • Dendritic cells
  • Porcine islets
  • Pig islets
  • In-vitro
  • Rat
  • Hypoxia
  • Transplantation
  • Expression
  • Reprograms

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

Show all authors Show less authors

Tools:

Journal Title:

Transplantation

Volume:

Volume 104, Number 2

Publisher:

, Pages 259-269

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2019 Wolters Kluwer Health, Inc. All rights reserved.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (https://creativecommons.org/licenses/by-nc/4.0/rdf).
Export to EndNote