Production of high‐quality islets from goettingen minipigs: Choice of organ preservation solution, donor pool, and optimal cold ischemia time

Steffen, Anȷa; Kiss, Thomas; Schmid, Janine; Schubert, Undine; Heinke, Sophie; Lehmann, Susann; Bornstein, Stefan R.; Ludwig, Barbara; Ludwig, Stefan

doi:10.1111/xen.12284

Cited by 10 publications

(6 citation statements)

References 38 publications

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“…For this study, female retired breeder minipigs with an average age of 3-4 y and average pregnancies of three to four were used ensuring for reproducible islet yields and quality (27). The procedure of pancreas organ retrieval has been described in detail previously (27). In brief, after premedication, the anesthesia was performed as total i.v.…”

Section: Methodsmentioning

confidence: 99%

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Ludwig

Steffen

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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101

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Transplantation of pancreatic islets for treating type 1 diabetes is restricted to patients with critical metabolic lability resulting from the need for immunosuppression and the shortage of donor organs. To overcome these barriers, we developed a strategy to macroencapsulate islets from different sources that allow their survival and function without immunosuppression. Here we report successful and safe transplantation of porcine islets with a bioartificial pancreas device in diabetic primates without any immune suppression. This strategy should lead to pioneering clinical trials with xenotransplantation for treatment of diabetes and, thereby, represents a previously unidentified approach to efficient cell replacement for a broad spectrum of endocrine disorders and other organ dysfunctions.

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Section: Methodsmentioning

confidence: 99%

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Ludwig

Steffen

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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101

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“…Therefore, a considerable islet loss and dysfunction usually happened during the preservation period. 3,4 Many efforts have been made to extend the islet ex vivo lifetime by exploiting the storage time, temperature, culture solution components, and methods. 5,6 Many studies compared the effect of temperature on the islet preservation, and there is still a lack of consensus.…”

Section: Introductionmentioning

confidence: 99%

Bilirubin Improves the Quality and Function of Hypothermic Preserved Islets by Its Antioxidative and Anti-inflammatory Effect

Yao

Jiang

Huang³

et al. 2019

Transplantation

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Background. Islet transplantation is a promising option for the treatment of type 1 diabetes. However, the current lack of practical techniques for the isolated islets preservation still hampers the advancement of life-saving islet transplantation. Islet suffers from internal or external stimuli-induced oxidative stress and subsequent inflammation during preservation, which leads to disappointing outcomes regarding islet yield, survival, and function. Reactive oxygen species (ROS) overproduction is the primary cause of oxidative stress that induces islet loss and dysfunction. Thus, in this article, we hypothesized that an endogenous antioxidant, bilirubin, that could efficiently scavenge ROS and inhibit inflammatory reactions could be beneficial for islet preservation. Methods. Herein, we studied the effect of bilirubin on the hypothermic preserved (4°C) islets and evaluate the islets viability, insulin secretory function, oxidative stress levels, and in vivo transplantation performance. Results. Bilirubin could prevent cellular damages during short-term preservation and maintain the cocultured islets viability and function. The protective role of bilirubin is associated with its antioxidative ability, which dramatically increased the activities of antioxidant enzymes (superoxide dismutase and glutathione peroxidase) and decreased the levels of ROS and malondialdehyde. Diabetic mice transplanted with bilirubin preserved islets were normoglycemic for 28 days, even overmatched the diabetic mouse transplanted with fresh islets. Mice receiving bilirubin cocultured islets required the least time to achieve normoglycemia among all groups and exhibited minimum inflammatory responses during the early transplantation stage. Conclusions. By utilizing bilirubin, we achieved highly viable and functional islets after hypothermic preservation to reverse diabetes in mice.

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“…500 IEQ (Islets Equivalent) adult pig islets or PBS were transplanted in the portal vein of NSGW41hIL7 mice that were humanized 24 weeks before. Islets were obtained from Goettingen minipigs (Ellgard) as described before 26, 27 . Human blood cell chimerism of used mice was 32-85%.…”

Section: Methodsmentioning

confidence: 99%

Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7

Coppin

Sundarasetty

Rahmig

et al. 2020

Preprint

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Key points 411.Increased intrathymic human T cell differentiation in the absence of 42 pathological lymphoproliferation in humanized NSGW41hIL7 mice. 43 44 2.Increased peripheral human T cell populations in NSGW41hIL7 mice making 45 the analysis of human regulatory T cells in vivo feasible. 46 47 48 49 50 Abstract 51Humanized mouse models have become increasingly valuable tools to study human 52 hematopoiesis and infectious diseases. However, human T cell differentiation 53 remains inefficient. We generated mice expressing human interleukin (IL-7), a critical 54 growth and survival factor for T cells, under the control of murine IL-7 regulatory 55 elements. After transfer of human cord blood-derived hematopoietic stem and 56 progenitor cells, transgenic mice on the NSGW41 background, termed 57NSGW41hIL7, showed elevated and prolonged human cellularity in the thymus while 58 maintaining physiological ratios of thymocyte subsets. As a consequence, numbers 59 of functional human T cells in the periphery were increased without evidence for 60 pathological lymphoproliferation or aberrant expansion of effector or memory-like T 61 cells. We conclude that the novel NSGW41hIL7 strain represents an optimized 62 mouse model for humanization to better understand human T cell differentiation in 63 vivo and to generate a human immune system with a better approximation of human 64 lymphocyte ratios. 65 knock-in of hIL-7 and hIL-15 on the NSG background displayed massive skewing 131 towards CD8 SP cells at the expense of DP thymocytes 17 , suggesting that tissue-132 specific expression of human cytokines alone is insufficient to promote human T cell

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Production of high‐quality islets from goettingen minipigs: Choice of organ preservation solution, donor pool, and optimal cold ischemia time

Cited by 10 publications

References 38 publications

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Favorable outcome of experimental islet xenotransplantation without immunosuppression in a nonhuman primate model of diabetes

Bilirubin Improves the Quality and Function of Hypothermic Preserved Islets by Its Antioxidative and Anti-inflammatory Effect

Enhanced differentiation of functional human T cells in NSGW41 mice with tissue-specific expression of human interleukin-7

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