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ACS Biomater Sci Eng. 2017 Jun 12;3(6):1051-1061. doi: 10.1021/acsbiomaterials.6b00814. Epub 2017 Apr 11.

Glucose-Stimulated Insulin Response of Silicon Nanopore-Immunoprotected Islets under Convective Transport.

Author information

1
Department of Bioengineering and Therapeutic Sciences, University of California-San Francisco, San Francisco, California 94158, United States.
2
Department of Surgery, University of California-San Francisco, San Francisco, California 94143, United States.

Abstract

Major clinical challenges associated with islet transplantation for type 1 diabetes include shortage of donor organs, poor engraftment due to ischemia, and need for immunosuppressive medications. Semipermeable membrane capsules can immunoprotect transplanted islets by blocking passage of the host's immune components while providing exchange of glucose, insulin, and other small molecules. However, capsules-based diffusive transport often exacerbates ischemic injury to islets by reducing the rate of oxygen and nutrient transport. We previously reported the efficacy of a newly developed semipermeable ultrafiltration membrane, the silicon nanopore membrane (SNM) under convective-driven transport, in limiting the passage of pro-inflammatory cytokines while overcoming the mass transfer limitations associated with diffusion through nanometer-scale pores. In this study, we report that SNM-encapsulated mouse islets perfused in culture solution under convection outperformed those under diffusive conditions in terms of magnitude (1.49-fold increase in stimulation index and 3.86-fold decrease in shutdown index) and rate of insulin secretion (1.19-fold increase and 6.45-fold decrease during high and low glucose challenges), respectively. Moreover, SNM-encapsulated mouse islets under convection demonstrated rapid glucose-insulin sensing within a physiologically relevant time-scale while retaining healthy islet viability even under cytokine exposure. We conclude that encapsulation of islets with SNM under convection improves islet in vitro functionality. This approach may provide a novel strategy for islet transplantation in the clinical setting.

KEYWORDS:

convection; diffusion; glucose-insulin kinetics; immunoisolation; silicon nanopore membranes (SNM)

Conflict of interest statement

Notes The authors declare the following competing financial interest(s): Dr. Shuvo Roy is a co-founder of Silicon Kidney, LLC. There are no competing interests or conflicts of interest related to the work presented in this manuscript for all authors.

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