A 1α,25-Dihydroxyvitamin D3 Analog Enhances Regulatory T-Cells and Arrests Autoimmune Diabetes in NOD Mice

Gregori, Silvia; Giarratana, Nadia; Smiroldo, Simona; Uskoković, Milan R.; Adorini, Luciano

doi:10.2337/diabetes.51.5.1367

Cited by 438 publications

(348 citation statements)

References 51 publications

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“…The principal physiological function of 1,25(OH) 2 D 3 is enhancing the absorption of calcium and phosphate from the intestinal tract, therefore positively regulating bone formation [9][10][11] . To date, several lines of epidemiological and experimental findings have supported the links of vitamin D with various conditions or diseases beyond bone health [3] , including muscle function [12,13] , autoimmune diseases [14] , cancer [15,16] , cardiovascular diseases (CVD) [17][18][19] , hypertension [20,21] , diabetes [22] , inflammatory diseases [23] , and all-cause mortality [24] , etc.…”

Section: General Roles Of Vitamin D In Physiological Conditions and Dmentioning

confidence: 99%

维生素d 在免疫反应和自身免疫性疾病特别是多发性硬化中的作用

Zhang

2010

Neurosci. Bull.

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Section: General Roles Of Vitamin D In Physiological Conditions and Dmentioning

confidence: 99%

维生素d 在免疫反应和自身免疫性疾病特别是多发性硬化中的作用

Zhang

2010

Neurosci. Bull.

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“…A number of researchers have identified strategies for the treatment and prevention of diabetes in NOD mice [21][22][23][24][25][26][27][28][29][30][31][32][33]. For example, anti-CD3 treatment in NOD mice formed the basis for a clinical trial of anti-CD3 monoclonal antibody therapy in human T1D models.…”

Section: Introductionmentioning

confidence: 99%

Differentiation and Transplantation of Functional Pancreatic Beta Cells Generated from Induced Pluripotent Stem Cells Derived from a Type 1 Diabetes Mouse Model

Jeon

Lim

Kim

et al. 2012

Stem Cells and Development

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The nonobese diabetic (NOD) mouse is a classical animal model for autoimmune type 1 diabetes (T1D), closely mimicking features of human T1D. Thus, the NOD mouse presents an opportunity to test the effectiveness of induced pluripotent stem cells (iPSCs) as a therapeutic modality for T1D. Here, we demonstrate a proof of concept for cellular therapy using NOD mouse-derived iPSCs (NOD-iPSCs). We generated iPSCs from NOD mouse embryonic fibroblasts or NOD mouse pancreas-derived epithelial cells (NPEs), and applied directed differentiation protocols to differentiate the NOD-iPSCs toward functional pancreatic beta cells. Finally, we investigated whether the NPE-iPSC-derived insulin-producing cells could normalize hyperglycemia in transplanted diabetic mice. The NOD-iPSCs showed typical embryonic stem cell-like characteristics such as expression of markers for pluripotency, in vitro differentiation, teratoma formation, and generation of chimeric mice. We developed a method for stepwise differentiation of NOD-iPSCs into insulin-producing cells, and found that NPE-iPSCs differentiate more readily into insulin-producing cells. The differentiated NPE-iPSCs expressed diverse pancreatic beta cell markers and released insulin in response to glucose and KCl stimulation. Transplantation of the differentiated NPE-iPSCs into diabetic mice resulted in kidney engraftment. The engrafted cells responded to glucose by secreting insulin, thereby normalizing blood glucose levels. We propose that NODiPSCs will provide a useful tool for investigating genetic susceptibility to autoimmune diseases and generating a cellular interaction model of T1D, paving the way for the potential application of patient-derived iPSCs in autologous beta cell transplantation for treating diabetes.

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“…The administration period for atorvastatin was comparable to that for other immunomodulatory treatments, such as 1α,25dihydroxyvitamin D 3 and nicotine, which have previously been reported to ameliorate or reduce diabetes incidence in mice [6,7], thus ruling out the possibility of an insufficient period of treatment.…”

mentioning

confidence: 67%

“…Previous studies have shown that 1α,25-dihydroxyvitamin D 3 or nicotine treatments in mice arrested the progression of type 1 diabetes with a concomitant, potentially related inhibition of Th1 CD4 + T cell infiltration of the pancreas [6,7]. To gain preliminary insight into the potential usefulness of statins in patients with prediabetes, we sought to determine whether atorvastatin could delay, or even prevent, diabetes onset in two experimental models of type 1 diabetes: multiple low-dose streptozotocin and spontaneous non-obese diabetic (NOD) mice.…”

mentioning

confidence: 99%