Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats

Balamurugan, A. N.; Nelson, Everette Jacob Remington; Ramakrishna, B. S.; Gunasekaran, S

doi:10.1111/j.1399-3089.2007.00409.x

Cited by 4 publications

(5 citation statements)

References 37 publications

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“…published the importance of establishing islet immunoisolation through magnetocapsules [34], but using our device we are achieving immunoprotection as demonstrated by the function of the islets through porcine C‐peptide and reduction in insulin requirements in more than 81% of the patients (more than 50% of patients remain with a reduction greater than 33%), and through low levels of antibodies already reported [20]. Perhaps our results could be improved if we use an immunosuppressive regimen [35]…”

Section: Discussionmentioning

confidence: 83%

Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets

Valdés-González

Rodríguez-Ventura²,

White

et al. 2010

Clinical and Experimental Immunology

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SummaryPancreas transplantation is an option to achieve better metabolic control and decrease chronic complications in patients with diabetes. Xenotransplantation becomes an important alternative. In this study, we show the clinical outcome of patients with type 1 diabetes transplanted with neonatal pig islets without immunosuppression. In a longitudinal study of 23 patients with type 1 diabetes, who received porcine islets between 2000 and 2004, we registered demographic and clinical characteristics every 3 months and chronic complications evaluation yearly. Porcine C-peptide was measured in urine samples under basal conditions and after stimulation with l-arginine. More than 50% were female, median current age was 20·8 years, median diabetes duration at transplantation 5·5 years, median current diabetes duration 11 years and median time post-transplantation 5·7 years. Their media of glycosylated haemoglobin reduced significantly after the first transplantation. Insulin doses remain with a reduction greater than 33% in more than 50% of the patients. Before transplantation, 14 of the 21 patients presented mild chronic complications and currently only two patients presented these complications. Porcine C-peptide was present in all urine samples under basal conditions and increased post-stimulation with l-arginine. These patients achieved an excellent metabolic control after the first transplantation. This could explain, as well as the remaining function of transplanted cells, the low frequency of chronic complications compared to patients with similar diabetes duration and age.

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Section: Discussionmentioning

confidence: 83%

Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets

Valdés-González

Rodríguez-Ventura²,

White

et al. 2010

Clinical and Experimental Immunology

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“…Balamurugan et al (2) described the effect of CsA, FK506 or prednisolone monotherapy on preventing monkey islet graft rejection after xenotransplantation in a rodent model. Histological examination indicated that monkey islets survived in the presence of continuous high-dose of immunosuppressive monotherapy in rodents.…”

Section: Discussionmentioning

confidence: 99%

Islet transplantation in rodents: do encapsulated islets really work?

Souza

Chaib

Lacerda

et al. 2011

Arq. Gastroenterol.

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-Context -Diabetes mellitus type I affects around 240 million people in the world and only in the USA 7.8% of the population.It has been estimated that the costs of its complications account for 5% to 10% of the total healthcare spending around the world. According to World Health Organization, 300 million people are expected to develop diabetes mellitus by the year 2025. The pancreatic islet transplantation is expected to be less invasive than a pancreas transplant, which is currently the most commonly used approach. Objectives -To compare the encapsulated and free islet transplantation in rodents looking at sites of islet implantation, number of injected islets, viability and immunosuppression. Methods -A literature search was conducted using MEDLINE/PUBMED and SCIELO with terms about islet transplantation in the rodent from 2000 to 2010. We found 2,636 articles but only 56 articles from 2000 to 2010 were selected. Results -In these 56 articles used, 34% were encapsulated and 66% were nonencapsulated islets. Analyzing both types of islets transplantation, the majority of the encapsulated islets were implanted into the peritoneal cavity and the nonencapsulated islets into the liver, through the portal vein. In addition, the great advantage of the peritoneal cavity as the site of islet transplantation is its blood supply. Both vascular endothelial cells and vascular endothelial growth factor were used to stimulate angiogenesis of the islet grafts, increasing the vascularization rapidly after implantation. It also has been proven that there is influence of the capsules, since the larger the capsule more chances there are of central necrosis. In some articles, the use of immunosuppression demonstrated to increase the life expectancy of the graft. Conclusion -While significant progress has been made in the islets transplantation field, many obstacles remain to be overcome. Microencapsulation provides a means to transplant islets without immunosuppressive agents and may enable the performance of xenotransplantation. The use of alternative donor sources, fewer islets per capsule and the appropriate deployment location, such as the peritoneal cavity, may give a future perspective to the application of immunoprotective capsules and viability in clinical practice. A variety of strategies, such as genetic engineering, co-encapsulation, improvement in oxygen supply or the establishment of hypoxia resistance will also improve the islet transplantation performance. It remains to be determined which combination of strategies with encapsulation can fulfill the promise of establishing a simple and safe transplantation as a cure for diabetes.

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“…Group I (control): Animals were fed standard balanced dietGroup II (steroid-treated animals): Animals were daily injected with prednisolone in a dose of 20 mg/kg for 2 weeks[13] and fed with balanced standard dietGroup III (steroid/barley-treated group): Animals were injected with prednisolone in the same dose and fed with barley mixed with balanced standard diet for 2 weeks. [14] Dose of barley was 53% of available diet for each animal.…”

Section: Methodsmentioning

confidence: 99%

“…Group II (steroid-treated animals): Animals were daily injected with prednisolone in a dose of 20 mg/kg for 2 weeks[13] and fed with balanced standard diet…”

Section: Methodsmentioning

confidence: 99%

The possible protective role of barley seeds on the spleen after administration of glucocorticoids in adult albino rats: A histological and immunohistochemical study

Shehata

Eldien

Meligy

et al. 2019

J Microsc Ultrastruct

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Background:Glucocorticoids (GCs) are the main treatment strategy in many autoimmune disease and inflammatory diseases; however, they have immunosuppressive effect on many organs. The barley seeds contain many antioxidant compounds, which may improve the antioxidant status and related physiological functions. Our aim in this work is to evaluate the possible protective role of barley seeds on some immune cells in the spleen against immunosuppressive effect of GCs in adult albino rats.Materials and Methods:Forty-five adult albino rats were equally divided into 3 groups. Group I: normal vehicle control (n = 15), Group II: steroid-treated animals (n = 15), and Group III: steroid/barley-treated group (n = 15). Specimens from spleen were processed for light and electron microscopy.Results:In steroid-treated group, the histological changes in white and red pulp were in the form of loss of architecture and wide empty spaces among the cells. Most of the cells showed degenerative change, dilatation of blood sinusoids, and deposition of fibrinoid material among the cells of the RP. However, multiple lysosomal bodies were observed in both dendritic and macrophage cells. These changes are improved in steroid/barley-treated group in the form of increasing the number and size of the lymphatic follicles. Most of the splenic cells regained normal structure. Dendritic cell marker CD86 and macrophage marker CD68 expression are increased.Conclusion:Barley protects the spleen tissues from steroid-induced structural changes; this could be mediated through its antioxidant effects, so barely is recommended as a healthy diet in patients consuming steroids.

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Effect of various immunosuppressive monotherapies on survival and histopathology of monkey islet xenografts in rats

Abstract: This study provided evidence for monkey islet survival after transplantation into rats receiving immunosuppressive monotherapy. Basic information on infiltrating cell types may be important in the study of xenograft rejection.

Cited by 4 publications

References 37 publications

Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets

Long-term follow-up of patients with type 1 diabetes transplanted with neonatal pig islets

Islet transplantation in rodents: do encapsulated islets really work?

The possible protective role of barley seeds on the spleen after administration of glucocorticoids in adult albino rats: A histological and immunohistochemical study

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