title: Differentiation of mouse nuclear transfer embryonic stem cells into functional pancreatic beta cells.
abstract: OBJECTIVE
  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
  These results demonstrate the potential of therapeutic cloning for cell therapy of type 1 diabetes in a mouse model.
authors.affiliation: Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, 100871, China.
authors.forename: W
authors.initials: W
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Bai
authors.forename: D
authors.initials: D
authors.lastname: Zhang
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.forename: J
authors.initials: J
authors.lastname: Yong
authors.forename: S
authors.initials: S
authors.lastname: Chen
authors.forename: M
authors.initials: M
authors.lastname: Ding
authors.forename: H
authors.initials: H
authors.lastname: Deng
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002999:Clone Cells / Q000166:cytology*; D003920:Diabetes Mellitus / Q000628:therapy; D053595:Embryonic Stem Cells / Q000166:cytology*; D015870:Gene Expression; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D053652:Nuclear Transfer Techniques; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007328:Insulin