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BACKGROUND: Etanercept is widely used as an antiinflammatory drug to improve engraftment after intraportal islet transplantation. In contrast to other immunosuppressive agents, very little is known about detrimental effects of etanercept on islets. The aim of this pilot study was to define the toxic range of etanercept. METHODS: Human islets isolated from 8 donors were cultured for 4-5 days at 37°C in culture medium supplemented with etanercept at concentrations from 2.5 to 40 μg/mL, corresponding to potential in vivo levels within the portal vein. After culture, islet equivalent (IEQ) yield, fragmentation index (islet number/IEQ), purity, viability, and stimulated insulin release (2 vs 20 mmol/L) were assessed and normalized to islets before culture. RESULTS: Yield (73 ± 8%) and viability (91 ± 4%) were highest with 5 μg/mL etanercept. Islet loss was evident when etanercept was ≥10 μg/mL (55 ± 7%; P < .05 vs control). Fragmentation (154 ± 34%; P < .05) was markedly increased and viability (81 ± 4%, P 10 μg/mL. The accumulation of cell debris at concentrations ≥20 μg/mL resulted in a significant reduction of islet purity (84 ± 3%; P 

Original publication

DOI

10.1016/j.transproceed.2017.11.002

Type

Journal article

Journal

Transplant Proc

Publication Date

12/2017

Volume

49

Pages

2327 - 2329

Keywords

Anti-Inflammatory Agents, Non-Steroidal, Cells, Cultured, Culture Media, Etanercept, Humans, Insulin, Insulin Secretion, Islets of Langerhans, Islets of Langerhans Transplantation, Maximum Tolerated Dose, Pilot Projects