Immunosuppression with FTY720 and cyclosporine A inhibits rejection of adult porcine islet xenografts in rats

Maeda, Akira; Goto, Masafumi; Zhang, J; Bennet, William; Groth, Carl‐Gustav; Korsgren, Olle; Wennberg, Lars

doi:10.1097/01.tp.0000061770.39569.7f

Cited by 24 publications

(23 citation statements)

References 23 publications

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“…In the past year, there have been numerous reports of the therapeutic potential of this compound in the context of autoimmune disorders and transplantation. FTY-720 appears to be a powerful immunosuppressant that, when used in combination with cyclosporine, abrogates xenograft rejection in several systems Koshiba et al, 2003;Maeda et al, 2003]. The protective effect is thought to be due to a decrease in lymphocyte infiltration into the xenograft site.…”

Section: Lysophospholipids and The Immune Systemmentioning

confidence: 92%

G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival

Radeff-Huang

Seasholtz

Matteo

et al. 2004

J of Cellular Biochemistry

176

178

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Agonist activation of a subset of G protein coupled receptors (GPCRs) stimulates cell proliferation, mimicking the better known effects of tyrosine kinase growth factors. Cell survival or apoptosis is also regulated via pathways initiated by stimulation of these same GPCRs. This review focuses on aspects of signaling by the lysophospholipid mediators, lysophosphatidic acid (LPA), and sphingosine 1 phosphate (S1P), which make these agonists uniquely capable of modulating cell growth and survival. The general features of GPCR coupling to specific G proteins, downstream effectors and signaling cascades are first reviewed. GPCR coupling to G(i) and Ras/MAPK or to G(q) and phospholipase generated second messengers are insufficient to regulate cell proliferation while G(12/13)/Rho engagement provides additional complementary signals required for cell proliferation. Survival is best predicted by coupling to G(i) pathways that regulate PI3K and Akt, but other signals generated through different G protein pathways are also implicated. The unique ability of LPA and S1P to concomitantly stimulate G(i), G(q), and G(12/13) pathways, given the proper complement of expressed LPA or S1P receptors, allows these receptors to support cell survival and proliferation. In pathophysiological situations, e.g., vascular disease, cancer, brain injury, and inflammation, components of the signaling cascade downstream of lysophospholipid receptors, in particular those involving Ras or Rho, may be altered. In addition, up or downregulation of LPA or S1P receptor subtypes, altering their ratio, and increased availability of the lysophospholipid ligands at sites of injury or inflammation, likely contribute to disease and may be important targets for therapeutic intervention.

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Section: Lysophospholipids and The Immune Systemmentioning

confidence: 92%

G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival

Radeff-Huang

Seasholtz

Matteo

et al. 2004

J of Cellular Biochemistry

176

178

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“…They found that this combination inhibited almost all morphological signs of pig-to-rat islet xenograft rejection for up to 24 days after transplantation (30) . Fotiadis et al (13) used mycophenolatemofetil (MMF) and CsA to check the positive or adverse effects of MMF as a single agent.…”

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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“…We report that, although treatment with FTY720 alone does not influence graft survival in other xenogenic transplantation models (32)(33)(34)(35)43), it significantly delays the rejection of rat-to-mouse xenogenic concordant corneal transplants.…”

mentioning

confidence: 92%

“…It inhibits lymphocyte emigration from the peripheral lymphoid organs and thymus (32)(33)(34)(35)(36), dramatically reducing the number of lymphocytes, especially T cells in the circulation (32,36,37), grafts (37,38) and tissues (30,39,40). Sequestration of lymphocytes in lymph nodes and Peyer's patches (41)-although less pronounced in mice (42)-is believed to be the dominant mode of action of FTY720, although long-term treatment also reduces the proliferative response of mouse lymphnode-derived T cells to alloantigens (42).…”

mentioning

confidence: 99%

FTY720 in Corneal Concordant Xenotransplantation

et al. 2005

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Immunosuppression with FTY720 and cyclosporine A inhibits rejection of adult porcine islet xenografts in rats

Abstract: Immunosuppression with FTY720 plus CsA inhibited almost all morphological signs of pig-to-rat islet xenograft rejection for up to 24 days after transplantation. Diabetic rats transplanted with APIs and immunosuppressed with FTY720 plus CsA remained normoglycemic for 53.0+/-15.8 days.

Cited by 24 publications

References 23 publications

G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival

G protein mediated signaling pathways in lysophospholipid induced cell proliferation and survival

Islet transplantation in rodents: do encapsulated islets really work?

FTY720 in Corneal Concordant Xenotransplantation

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