Expression and Immune Response to Islet Antigens following Treatment with Low Doses of Streptozotocin in H-2dMice

Herold, Kevan C.; Baumann, Elizabeth; Vezys, Vaiva; Buckingham, F

doi:10.1006/jaut.1996.0108

Cited by 12 publications

(7 citation statements)

References 35 publications

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“…This protocol results in insulitis and in the destruction of pancreatic beta-cells [37], [34], [35]. As expected, animals gradually became hyperglycemic ( diabetic , Figure 2) [28], [36], in association with a massive lost of pancreatic islets and hypoinsulinemia ( diabetic , Figure 3) [28].…”

Section: Resultsmentioning

confidence: 52%

The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells

Ezquer

Simon

et al. 2011

PLoS ONE

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Type 1 diabetes mellitus (T1D) is due to autoimmune destruction of pancreatic beta-cells. Previously, we have shown that intravenously administered bone marrow-derived multipotent mesenchymal stromal cells (MSCs) allows pancreatic islet recovery, improves insulin secretion and reverts hyperglycemia in low doses streptozotocin (STZ)-induced diabetic mice. Here we evaluate whether insulin prophylaxis and the administration of a second dose of cells affect the antidiabetic therapeutic effect of MSC transplantation. Insulitis and subsequent elimination of pancreatic beta-cells was promoted in C57BL/6 mice by the injection of 40 mg/kg/day STZ for five days. Twenty-four days later, diabetic mice were distributed into experimental groups according to if they received or not insulin and/or one or two doses of healthy donor-derived MSCs. Three and half months later: glycemia, pancreatic islets number, insulinemia, glycated hemoglobin level and glucose tolerance were determined in animals that did not received exogenous insulin for the last 1.5 months. Also, we characterized MSCs isolated from mice healthy or diabetic. The therapeutic effect of MSC transplantation was observed in diabetic mice that received or not insulin prophylaxis. Improvements were similar irrespective if they received one or two doses of cells. Compared to MSCs from healthy mice, MSCs from diabetic mice had the same proliferation and adipogenic potentials, but were less abundant, with altered immunophenotype and no osteogenic potential.Our preclinical results should be taken into account when designing phase II clinical trials aimed to evaluate MSC transplantation in patients with T1D. Cells should be isolated form healthy donor, insulin prophylaxis could be maintained and a second dose, after an elapse of two months, appears unnecessary in the medium-term.

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Section: Resultsmentioning

confidence: 52%

The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells

Ezquer

Simon

et al. 2011

PLoS ONE

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“…Some investigators believe that the generation of IDDM only relates to partial invasion of lymphocytes in islet cells and cytokine expression [22]. The results of this paper provide evidence of altered lymphocytes subsets and cytokine expression in splenocytes of IDDM mice.…”

Section: Discussionmentioning

confidence: 83%

Effect of aSiraitia grosvenori extract containing mogrosides on the cellular immune system of type 1 diabetes mellitus mice

Xiang-yang¹,

Chen

Liu

et al. 2006

Mol. Nutr. Food Res.

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The purpose of this study was to observe the islet changes of pancreas in insulin-dependent diabetes mellitus (IDDM) mice in comparison to normal mice after application of an extract from Siraitia grosvenori fruits containing mogrosides, in particular, mogroside V. We hypothesized that mogroside extract (MG) attenuates the severity of alloxan-induced IDDM by effects on the immune system. Our data show that IDDM mice exhibited significant injury to pancreatic islets cells, which were atrophic. In addition, alloxan induced a notable increase in the expression of CD8+ lymphocytes to form a dramatic decrease in CD4+/CD8+ ratio (while CD4+ was unchanged). MG, administered to normal and experimental diabetic mice for 4 wk, effectively attenuated the early clinical symptoms, biochemical abnormalities, and pathological damages in pancreatic islets. Furthermore, at low dose, MG regulated the immune imbalance observed in alloxan-induced IDDM mice by up-regulating the CD4+ T-lymphocyte subsets and CD4/CD8 ratio, and altering the intracellular cytokine profiles. The expression of the pro-inflammatory Th1 cytokines: IFN-gamma, TNF-alpha in splenic lymphocytes was altered toward a beneficial Th2 pattern. MG therapy had no effect on normal mice, except that low dosage MG could up-regulate the IL-4 expression levels. The results revealed that MG exhibited antidiabetic effects presumably due to the presence of mogrosides.

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“…Since an inflammatory and an autoimmune component in the STZ model has not been reported clearly further research should focus on role of WJMSC and WJMSC islet derivatives in a physiological auto-immune diabetes scenario. The inflammatory component of physiological diabetes can be mimicked by changing the STZ dosage [93]. Undifferentiated BMMSCs when injected in STZ diabetic model rescued the glucose homeostasis [reviewed in 2].…”

Section: Activation/differentiation State Of the Interacting Immune Cmentioning

confidence: 99%

Wharton's Jelly Mesenchymal Stem Cells as Off-The-Shelf Cellular Therapeutics: A Closer Look into their Regenerative and Immunomodulatory Properties

Prasanna¹

2011

TOTERMJ

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Mesenchymal stem/stromal cells (MSCs) are isolated from most post-natal tissues and are broadly reported to have similar immuno-phenotype, mesenchymal lineage-differentiation potential and bio-distribution in peri-vascular niches. Thus, several stromal substitutes of bone marrow mesenchymal stem cells (BMMSCs) are being considered for regenerative therapy. Wharton's jelly mesenchymal stem cells (WJMSCs) seem to be the most promising alternative because of easy donor accessibility, high proliferative capacity and greater sample to sample identity.Recent in vitro and in vivo evidences also support the usage of WJMSCs in tissue repair and regeneration. Key to these observations is secretion of trophic and immune regulatory factors, which aid repair, and resolution of injury. In order to extrapolate these results for clinical usage key questions that need to be addressed are: extrapolation of "allogeneic" transplantation ability of BMMSCs to WJMSCs, survival of allogeneic/xenogeneic WJMSCs in transplantation scenario and actual mechanisms of immune-modulation in an "inflammatory" setting. This review focuses on comparing the in vitro and in vivo studies on immune regulatory properties of WJMSCs and BMMSCs and speculates the usage of WJMSCs for immuno-modulation in a disease scenario. Despite commonalities, different tissue-derived MSCs are reported to have unique gene expression signatures. We would evaluate whether WJMSCs have unique inherent properties, owing to their bio-distribution and primitiveness, as compared to BMMSCs. Further, we debate whether these differences remain conserved on in vitro propagation and impact the immune properties of WJMSCs and speculate the pros and cons of using WJMSCs for allogeneic transplantation.

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Expression and Immune Response to Islet Antigens following Treatment with Low Doses of Streptozotocin in H-2dMice

Cited by 12 publications

References 35 publications

The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells

The Antidiabetic Effect of MSCs Is Not Impaired by Insulin Prophylaxis and Is Not Improved by a Second Dose of Cells

Effect of aSiraitia grosvenori extract containing mogrosides on the cellular immune system of type 1 diabetes mellitus mice

Wharton's Jelly Mesenchymal Stem Cells as Off-The-Shelf Cellular Therapeutics: A Closer Look into their Regenerative and Immunomodulatory Properties

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