Abstract
AimsRecent studies suggest that decreasing oxidative stress is crucial to achieve successful islet transplantation. Thioredoxin-1 (TRX), which is a multifunctional redox-active protein, has been reported to suppress oxidative stress. Furthermore, it also has anti-inflammatory and anti-apoptotic effects. In this study, we investigated the effects of TRX on early graft loss after islet transplantation.MethodsIntraportal islet transplantation was performed for two groups of streptozotocin-induced diabetic mice: a control and a TRX group. In addition, TRX-transgenic (Tg) mice were alternately used as islet donors or recipients.ResultsThe changes in blood glucose levels were significantly lower in the TRX group compared with the TRX-Tg donor and control groups (p<0.01). Glucose tolerance and the residual graft mass were considerably better in the TRX group. TRX significantly suppressed the serum levels of interleukin-1β (p<0.05), although neither anti-apoptotic nor anti-chemotactic effects were observed. Notably, no increase in the 8-hydroxy-2′-deoxyguanosine level was observed after islet infusion, irrespective of TRX administration.ConclusionsThe present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment. In contrast, TRX administration to the recipients exerts protective effects on transplanted islet grafts by suppressing the serum levels of interleukin-1β. However, TRX alone appears to be insufficient to completely prevent early graft loss after islet transplantation. We therefore propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation.
Highlights
Since the development of the Edmonton protocol, islet transplantation has become an effective option for the clinical treatment of type 1 diabetic patients [1]
The present study demonstrates that overexpression of TRX on the islet grafts is not sufficient to improve engraftment
We propose that a combination of TRX and other anti-inflammatory treatments represents a promising regimen for improving the efficacy of islet transplantation
Summary
Since the development of the Edmonton protocol, islet transplantation has become an effective option for the clinical treatment of type 1 diabetic patients [1]. Several donor pancreases are still needed to cure each diabetic patient. The instant blood-mediated inflammatory reaction (IBMIR) that occurs as an innate immune response, characterized by activation of both the coagulation and complement cascades, is a major cause of islet graft loss [2,3,4]. We and others have demonstrated that tissue factor (TF) and monocyte chemoattractant protein-1 (MCP-1) expressed on the grafted islets elicit the IBMIR [4,5,6,7,8,9]. To achieve successful outcomes of islet transplantation from a single donor organ, avoidance of the IBMIR is necessary
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