Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research

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

doi:10.1111/xen.12255

Cited by 12 publications

(8 citation statements)

References 30 publications

(37 reference statements)

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“…Insulin glulisine was administered before feeding and for correcting hyperglycemia according to BG readings (2-4 IU/regular meal; 1 IU for lowering BG by 1 mmol/L; target BG level of 8 mmol/L). One week after pancreatectomy, the animals received a single dose of streptozotocin of 80 mg/kg BW to induce complete insulin deficiency (28), which was proven by negative monkey-specific C-peptide measurement during ivGTT.…”

Section: Days Relative To Transplantmentioning

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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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: Days Relative To Transplantmentioning

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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“…Furthermore, the porcine models can also be used for the testing of new genetic therapy approaches. Last but not least, there are the surgical methods; meaning the complete removal of the pancreas (pancreatectomy), which are rather used as models for β-cell transplantation (85,86). While this simulates a complete loss of β-cells, it also loses the endocrine effect of the pancreas (87).…”

Section: Porcine Modelsmentioning

confidence: 99%

Research('s) Sweet Hearts: Experimental Biomedical Models of Diabetic Cardiomyopathy

Richter

Hinkel

2021

Front. Cardiovasc. Med.

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Diabetes and the often accompanying cardiovascular diseases including cardiomyopathy represent a complex disease, that is reluctant to reveal the molecular mechanisms and underlying cellular responses. Current research projects on diabetic cardiomyopathy are predominantly based on animal models, in which there are not only obvious advantages, such as genetics that can be traced over generations and the directly measurable influence of dietary types, but also not despisable disadvantages. Thus, many studies are built up on transgenic rodent models, which are partly comparable to symptoms in humans due to their genetic alterations, but on the other hand are also under discussion regarding their clinical relevance in the translation of biomedical therapeutic approaches. Furthermore, a focus on transgenic rodent models ignores spontaneously occurring diabetes in larger mammals (such as dogs or pigs), which represent with their anatomical similarity to humans regarding their cardiovascular situation appealing models for testing translational approaches. With this in mind, we aim to shed light on the currently most popular animal models for diabetic cardiomyopathy and, by weighing the advantages and disadvantages, provide decision support for future animal experimental work in the field, hence advancing the biomedical translation of promising approaches into clinical application.

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“…The spleen contains large quantities of B cells involved in antibody production, and in pigs, in particular its volume is extremely large. Splenectomy in pigs is the subject of particular attention for 4 liver regeneration 8 that changes perfusion in the portal region, and for the production of diabetic model animals 9 . In splenectomy in pigs, it is important that the splenic body omental vessels, short gastric vessels, and the splenic vessels, all of which are large, are carefully ligated (Fig.…”

Section: B: Splenectomymentioning

confidence: 99%

Surgically produced, controllable immunocompromised pigs

Kobayashi¹,

Maki²,

Igaki³

et al. 2019

Preprint

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Majority of research on human regenerative medicine has focused on the use of human mature cells/tissues and stem cell derived products. To ensure their safety and efficacy for clinical application, preclinical testing in large animals such as pigs, using pre-clinical and clinical matching protocols, is required. However, presently, there is no universal, stable, adjustable immunosuppressed pig model in which human regenerative cell and tissue products may be evaluated. Consequently, we established a controllable immunocompromised pig model by surgical excision of immune organs and varying the administration of immunosuppressive agents based on the physical condition and pharmacokinetic profile. Here, we describe the precise experimental procedure and provide information on immunosuppression therapies in different breeds of laboratory pigs. We provide practical information for the production of operational SCID pigs. We believe that our procedure may be immediately implemented in human-to-pig experiments, resulting in cost-benefit perspectives and furthering the development of new regenerative medicine.

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Diabetes induction by total pancreatectomy in minipigs with simultaneous splenectomy: a feasible approach for advanced diabetes research

Cited by 12 publications

References 30 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

Research('s) Sweet Hearts: Experimental Biomedical Models of Diabetic Cardiomyopathy

Surgically produced, controllable immunocompromised pigs

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