Abstract
Recurrence of autoimmunity and allograft rejection represent major challenges that impact the success of islet transplantation. Despite the remarkable improvements achieved in immunosuppression strategies after the publication of the Edmonton protocol, long-term data of intra-hepatic islet transplantation show a gradual decline in beta-cell function. Therefore, there is a growing interest in the investigation of novel, safe and effective anti-inflammatory and immunomodulatory strategies able to promote long-term islet graft survival and notable improvements in clinical outcomes of islet transplant recipients. Vitamin D has been shown to exert anti-inflammatory and immunomodulatory effects. Pre-clinical studies investigating the use of vitamin D and its analogs (alone or in combination with immunosuppressive agents and/or other anti-inflammatory agents, such as omega-3 polyunsaturated fatty acids) showed beneficial results in terms of islet graft survival and prevention of recurrence of autoimmunity/allograft rejection in animal models of syngeneic and allogeneic islet transplantation. Moreover, epidemiologic studies demonstrated that vitamin D deficiency is highly prevalent after solid organ transplantation (e.g., heart, liver or kidney transplantation). However, studies that critically assess the prevalence of vitamin D deficiency among islet transplant recipients have yet to be conducted. In addition, prospective studies aimed to address the safety and efficacy of vitamin D supplementation as an adjuvant immunomodulatory strategy in islet transplant recipients are lacking and are therefore awaited in the future.
Highlights
Type 1 diabetes (T1D) is a chronic, organ-specific autoimmune disease characterized by the progressive destruction of pancreatic beta cells, which results in lifelong dependence on Nutrients 2019, 11, 2937; doi:10.3390/nu11122937 www.mdpi.com/journal/nutrientsNutrients 2019, 11, 2937 exogenous insulin
These events have been shown to result in a loss of approximately 60% of transplanted islets, which has been attributed to apoptosis and necrosis occurring during the first days post-transplantation [13,16]
Pre-clinical evidence suggests that vitamin D and its analogs are safe and effective immunomodulatory agents in animal models of syngeneic and allogeneic islet transplantation
Summary
Type 1 diabetes (T1D) is a chronic, organ-specific autoimmune disease characterized by the progressive destruction of pancreatic beta cells, which results in lifelong dependence on Nutrients 2019, 11, 2937; doi:10.3390/nu11122937 www.mdpi.com/journal/nutrientsNutrients 2019, 11, 2937 exogenous insulin. Showed that only a minority of T1D patients (approximately 10%) who underwent islet transplantation were able to maintain insulin independence over a 5-year follow-up period, despite ongoing evidence of persistent graft function, as indicated by restored C-peptide secretion [8]. Intra-hepatic islet transplantation leads to thrombosis and liver ischemia due to islet entrapment in the liver sinusoids and subsequent activation of Kupffer cells and sinusoidal endothelial cells [14,15]. In animal models, these events have been shown to result in a loss of approximately 60% of transplanted islets, which has been attributed to apoptosis and necrosis occurring during the first days post-transplantation [13,16]
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