W Jiang1, Z Bai, D Zhang, Y Shi, J Yong, S Chen, M Ding, H Deng. 1. Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, 100871, China.
Abstract
AIMS/HYPOTHESIS: Therapeutic cloning has been reported to have potential in the treatment of several degenerative diseases. However, it has yet to be determined whether mouse nuclear transfer-embryonic stem cells (NT-ESCs) can be differentiated into pancreatic beta cells and used to reverse diabetes in an animal model. METHODS: We first used the somatic nuclear transfer technique to generate mouse NT-ESCs and then developed a chemically defined stepwise protocol to direct the NT-ESCs into functional pancreatic beta cells. We examined the gene expression pattern of the differentiated NT-ESCs and transplanted the NT-ESC-derived insulin-producing cells into recipient diabetic mice. RESULTS: Four mouse NT-ESC lines were first established using an improved nuclear transfer technique and insulin-producing cells were efficiently generated from NT-ESCs by mimicking pancreatic in vivo development. Most of the insulin-producing cells that we generated co-produced pancreatic and duodenal homeobox 1, but not glucagon at the final stage of this differentiation method, which differed from the insulin and glucagon co-production reported by other groups. The differentiated NT-ESCs were able to release insulin in response to glucose stimuli and normalise the blood glucose level of diabetic mice for at least 2 months. CONCLUSIONS/ INTERPRETATION: These results demonstrate the potential of therapeutic cloning for cell therapy of type 1 diabetes in a mouse model.
AIMS/HYPOTHESIS: Therapeutic cloning has been reported to have potential in the treatment of several degenerative diseases. However, it has yet to be determined whether mouse nuclear transfer-embryonic stem cells (NT-ESCs) can be differentiated into pancreatic beta cells and used to reverse diabetes in an animal model. METHODS: We first used the somatic nuclear transfer technique to generate mouse NT-ESCs and then developed a chemically defined stepwise protocol to direct the NT-ESCs into functional pancreatic beta cells. We examined the gene expression pattern of the differentiated NT-ESCs and transplanted the NT-ESC-derived insulin-producing cells into recipient diabeticmice. RESULTS: Four mouse NT-ESC lines were first established using an improved nuclear transfer technique and insulin-producing cells were efficiently generated from NT-ESCs by mimicking pancreatic in vivo development. Most of the insulin-producing cells that we generated co-produced pancreatic and duodenal homeobox 1, but not glucagon at the final stage of this differentiation method, which differed from the insulin and glucagon co-production reported by other groups. The differentiated NT-ESCs were able to release insulin in response to glucose stimuli and normalise the blood glucose level of diabeticmice for at least 2 months. CONCLUSIONS/ INTERPRETATION: These results demonstrate the potential of therapeutic cloning for cell therapy of type 1 diabetes in a mouse model.
Authors: J B Cibelli; S L Stice; P J Golueke; J J Kane; J Jerry; C Blackwell; F A Ponce de León; J M Robl Journal: Science Date: 1998-05-22 Impact factor: 47.728
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