Differentiation of mouse nuclear transfer embryonic stem cells into functional pancreatic beta cells.
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.
Jiang
W
W
Key Laboratory of Cell Proliferation and Differentiation of the Ministry of Education, College of Life Sciences, Peking University, Beijing, 100871, China.
Bai
Z
Z
Zhang
D
D
Shi
Y
Y
Yong
J
J
Chen
S
S
Ding
M
M
Deng
H
H
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
D007328:Insulin