Oxygenation strategies for encapsulated islet and beta cell transplants

Klearchos K. Papas, Hector De Leon, Thomas M. Suszynski, Robert C. Johnson

Research output: Contribution to journalReview articlepeer-review

53 Scopus citations

Abstract

Human allogeneic islet transplantation (ITx) is emerging as a promising treatment option for qualified patients with type 1 diabetes. However, widespread clinical application of allogeneic ITx is hindered by two critical barriers: the need for systemic immunosuppression and the limited supply of human islet tissue. Biocompatible, retrievable immunoisolation devices containing glucose-responsive insulin-secreting tissue may address both critical barriers by enabling the more effective and efficient use of allogeneic islets without immunosuppression in the near-term, and ultimately the use of a cell source with a virtually unlimited supply, such as human stem cell-derived β-cells or xenogeneic (porcine) islets with minimal or no immunosuppression. However, even though encapsulation methods have been developed and immunoprotection has been successfully tested in small and large animal models and to a limited extent in proof-of-concept clinical studies, the effective use of encapsulation approaches to convincingly and consistently treat diabetes in humans has yet to be demonstrated. There is increasing consensus that inadequate oxygen supply is a major factor limiting their clinical translation and routine implementation. Poor oxygenation negatively affects cell viability and β-cell function, and the problem is exacerbated with the high-density seeding required for reasonably-sized clinical encapsulation devices. Approaches for enhanced oxygen delivery to encapsulated tissues in implantable devices are therefore being actively developed and tested. This review summarizes fundamental aspects of islet microarchitecture and β-cell physiology as well as encapsulation approaches highlighting the need for adequate oxygenation; it also evaluates existing and emerging approaches for enhanced oxygen delivery to encapsulation devices, particularly with the advent of β-cell sources from stem cells that may enable the large-scale application of this approach.

Original languageEnglish (US)
Pages (from-to)139-156
Number of pages18
JournalAdvanced Drug Delivery Reviews
Volume139
DOIs
StatePublished - Jan 15 2019
Externally publishedYes

Bibliographical note

Funding Information:
This review manuscript was supported in part by grants from the Juvenile Diabetes Research Foundation (JDRF) and the National Institutes of Health (NIH) , United States ( NIH, National Institute of Diabetes and Digestive and Kidney Diseases : 1DP3DK106933-01 ; JDRF : 3-SRA-2016-254-S-B , 3-SRA-2015-40-Q-R , 2-SRA-2014-289-Q-R and 5-2013-141 ).

Funding Information:
The authors would like to thank Chan A. Ion, Leah Steyn, Steven Neuenfeldt and Catherine Min for providing assistance with artwork, and Stathis Avgoustiniatos for helpful discussions on mathematical diffusion reaction models related to oxygen delivery to encapsulation devices. This review manuscript was supported in part by grants from the Juvenile Diabetes Research Foundation (JDRF) and the National Institutes of Health (NIH), United States (NIH, National Institute of Diabetes and Digestive and Kidney Diseases: 1DP3DK106933-01; JDRF: 3-SRA-2016-254-S-B, 3-SRA-2015-40-Q-R, 2-SRA-2014-289-Q-R and 5-2013-141). Klearchos K. Papas is the co-founder and CEO of Procyon Technologies, LLC, a startup company focused on the development of oxygenated cell encapsulation devices. Hector De Leon, Thomas M. Suszynski, and Robert C. Johnson have no competing financial interests to disclose.

Publisher Copyright:
© 2019

Keywords

  • Devices
  • Diabetes
  • Encapsulation
  • Islet transplantation
  • Oxygen

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