Production of genetically modified pigs expressing human insulin and C-peptide as a source of islets for xenotransplantation
| Autor: | Bumrae Cho, Eun-Jin Lee, J. T. Kang, Dal-Young Ji, Sang-Hoon Lee, Ghangyong Kim, Sun Mi Ahn |
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| Rok vydání: | 2019 |
| Předmět: |
Blood Glucose
0106 biological sciences 0301 basic medicine endocrine system medicine.medical_specialty Swine Xenotransplantation medicine.medical_treatment Transgene Transplantation Heterologous Islets of Langerhans Transplantation Biology 01 natural sciences Animals Genetically Modified Gene Knockout Techniques 03 medical and health sciences chemistry.chemical_compound Diabetes mellitus Internal medicine Diabetes Mellitus Genetics medicine Animals Humans Insulin Proinsulin geography geography.geographical_feature_category C-Peptide C-peptide Fibroblasts Islet medicine.disease Transplantation 030104 developmental biology Endocrinology chemistry Animal Science and Zoology Genetic Engineering Agronomy and Crop Science 010606 plant biology & botany Biotechnology |
| Zdroj: | Transgenic Research. 28:549-559 |
| ISSN: | 1573-9368 0962-8819 |
| Popis: | Islet xenotransplantation is a promising treatment for type I diabetes. Numerous studies of islet xenotransplantation have used pig-to-nonhuman primate transplantation models. Some studies reported long-term survival and successful function of porcine islets in diabetic monkeys. Genetic engineering techniques may improve the survival and function of porcine islets. A recent study reported the generation of transgenic pigs expressing human insulin rather than porcine insulin by changing one amino acid at the end of the β-chain in insulin. However, C-peptide from pigs still existed. In this study, we generated transgenic pigs expressing human proinsulin to express human insulin and C-peptide using fibroblasts from proinsulin knockout pigs as donor cells for somatic cell nuclear transfer. Eleven live piglets were delivered from three surrogates and characterized to confirm the genotype and phenotype of the generated piglets. Genotype analysis of the generated piglets showed that five of the eleven piglets contained the human proinsulin gene. Insulin expression was confirmed in the serum and pancreas in two of the five piglets. C-peptide derived from human proinsulin was also confirmed by liquid chromatography tandem mass spectrometry. Non-fasting blood glucose level was measured to verify the function of the insulin derived from the human proinsulin. Two piglets expressing insulin showed normal glucose levels similar to that in the wild-type control. In conclusion, human insulin- and C-peptide-expressing pigs without porcine insulin and C-peptide were successfully established. These pigs can be used as a source of islets for islet xenotransplantation. |
| Databáze: | OpenAIRE |
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