Diabetic Rats Transplanted With Adult Porcine Islets and Immunosuppressed With Cyclosporine A, Mycophenolate Mofetil, and Leflunomide Remain Normoglycemic for Up to 100 Days1

Wennberg, Lars; Song, Z; Bennet, William; Zhang, Jiang; Nava, S; Sundberg, B; Bari, S; Groth, Carl G.; Korsgren, Olle

doi:10.1097/00007890-200104270-00002

Cited by 50 publications

(15 citation statements)

References 69 publications

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“…with earlier reports (29,32), and led to our standard dose of 15,000-30,000 IE/kg. However, transplanting an ex- One recipient had returned to hyperglycemia on day 8 after two consecutive blood glucose measurements of ≥20 mM/L (dotted line).…”

Section: Immunosuppression Recipient Ratssupporting

confidence: 88%

“…Recalculated on a per day baa good quality graft, especially of porcine islets, have in many instances contributed substantially. Apart from a sis, rats in the present study received ±6.5 mg/kg/day, which is less than half of the dose in the Swedish studies series of sparsely documented studies (13,20,30), two recent articles reported successful transplantation of (15 mg/kg/day) in which additionally substantial dosages of MMF and leflunomide (32) or FTY720 (21) adult porcine islets in the rat (21,32). In both studies the graft survivals were alike and remarkably similar to the were given daily.…”

Section: Immunosuppression Recipient Ratsmentioning

confidence: 79%

“…Culture was only for 1 day and there were ma- tion of the graft. In the reported studies, islets were cultured for only 1 day and it was indicated in one of these studies that in vitro function was not optimal at that moment and clearly better on day 8 (29,32), suggesting that tively short survival times seen in some of these recipi- devoid of remnants after the long-term culturing. HowDiabetic recipient rats were transplanted with porcine islets under the ever, no effect on graft survival was found.…”

Section: Immunosuppression Recipient Ratsmentioning

confidence: 99%

“…no weight gain was found (7,20,(31)(32)(33) or even substantial weight loss was seen (31, 33). Yet all grafts survived long term, notwithstanding that skin grafts are generally considered highly immunoHistological analysis revealed some intriguing findings.…”

Section: Immunosuppression Recipient Ratsmentioning

confidence: 99%

“…In most studies on adult porcine islet xenotransplantation to the rat, islets are transplanted lets (26). The aim of the present study was to evaluate the directly after isolation (7,21,30) or after a few days of culturing (29,32).…”

Section: Introductionmentioning

confidence: 99%

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Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

et al. 2010

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To evaluate whether further improvement in porcine islet xenotransplantation is feasible, a number of questions were addressed. Earlier we showed significant improvement in the nude mouse of the porcine islets by selection through long-term culture. Now these islets were tested in the stringent pig-to-rat model. Islets were isolated from adult pigs, cultured for 1.5-3 weeks and transplanted to rats. Possible rejection mechanisms were assessed by interference of the cellular response with cyclosporine A (CsA), blocking macrophages with gadolinium chloride (GdCl), and suppressing the humoral response with cyclophosphamide. Modifications in graft size and condition were analyzed. Untreated control recipients showed primary nonfunction (PNF). CsA treatment could fully overcome PNF and resulted in graft survival from 10 to over 134 days. Rejection was the main cause of function loss. Although rejection could not be prevented by intensifying the induction therapy, increased maintenance immunosuppression effectively blocked rejection, albeit at the expense of toxicity. Blocking the humoral response was ineffective; all grafts showed PNF. In contrast, depletion of macrophages fully prevented PNF. Combination of GdCl and CsA gave no additional effect, and grafts were rejected between 57 and 162 days. Generally, graft survivals were similar to those reported in the literature; however, long-term cultured islets required much less maintenance immunosuppression. Cessation of graft function was not always due to rejection; in some cases "islet exhaustion" was found, possibly caused by discrepancy between the graft size and the rapidly growing recipient. Neither the presence of damaged islet tissue in the graft nor the size of the graft exerted any influence on graft survival. On rejection, no real infiltration of the graft was seen; destruction gradually processed from the outside. The good functional capability of the cultured islets was illustrated by disappearance of the clinical symptoms and increase in body weight, which almost doubled in the long-term survivors.

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Section: Immunosuppression Recipient Ratssupporting

confidence: 88%

Section: Immunosuppression Recipient Ratsmentioning

confidence: 79%

Section: Immunosuppression Recipient Ratsmentioning

confidence: 99%

Section: Immunosuppression Recipient Ratsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

et al. 2010

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Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

Javeed

Zhao²

2008

Inflamm. res.

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Macrophage migration inhibitory factor (MIF) functions as a pleiotropic protein, participating in inflammatory and immune responses. MIF was originally discovered as a lymphokine involved in delayed hypersensitivity and various macrophage functions, including production of proinflammatory cytokines, glucocorticoid-induced immunomodulator, and natural killer cell inhibitory factor (NKIF), regulation of toll-like receptor expression, adherence and phagocytosis of macrophages, as well as induction of metalloproteinase. Therefore MIF is considered as a potential target protein in many pathophysiological states. In this review, considering the protein structure and the acting mechanisms of MIF, we mainly discuss the important role of MIF in pathogenesis of inflammatory diseases and graft rejection.

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Biocompatibility and function of microencapsulated pancreatic islets

et al. 2006

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Diabetic Rats Transplanted With Adult Porcine Islets and Immunosuppressed With Cyclosporine A, Mycophenolate Mofetil, and Leflunomide Remain Normoglycemic for Up to 100 Days1

Abstract: Well-functioning APIs can be isolated in large numbers. API xenografts can be protected from rejection and can maintain an adequate function for up to 100 days, in rats immunosuppressed with CsA+MMF+LEF.

Cited by 50 publications

References 69 publications

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

Transplantation of Long-term Cultured Porcine Islets in the Rat: Prolonged Graft Survival and Recipient Growth on Reduced Immunosuppression

Macrophage-migration inhibitory factor: role in inflammatory diseases and graft rejection

Biocompatibility and function of microencapsulated pancreatic islets

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