Glucose-Stimulated Insulin Response of Silicon Nanopore-Immunoprotected Islets under Convective Transport
| Autor: | Jaehyun Park, Andrew M. Posselt, Tejal A. Desai, Shang Song, Shuvo Roy, Qizhi Tang, Raymond Yeung |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
glucose-insulin kinetics medicine.medical_specialty endocrine system Materials science medicine.medical_treatment Ischemia Biomedical Engineering 030209 endocrinology & metabolism Bioengineering Autoimmune Disease Article Biomaterials 03 medical and health sciences 0302 clinical medicine Internal medicine medicine Nanotechnology Semipermeable membrane convection Metabolic and endocrine geography immunoisolation Transplantation geography.geographical_feature_category Insulin diffusion Diabetes medicine.disease Islet Nanopore Ultrafiltration (renal) 030104 developmental biology Endocrinology Membrane Biophysics silicon nanopore membranes |
| Zdroj: | ACS biomaterials science & engineering, vol 3, iss 6 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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