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Regenerative medicine

including cell-replacement strategies

may have an important role in the treatment of type 1 diabetes which is associated with decreased islet cell mass.To date

significant progress has been made in generating insulin-secretingβcells from pluripotent mouse embryonic stem cells（ESCs）.The aim of this study is to explore the potential of regulating the differentiation of ESCs into pancreatic endocrine cells capable of synthesizing the pancreatic hormones including insulin

glucagon

somatostatin and pancreatic polypeptide under proper conditions. Undifferentiated ES cell line was stably transfected with mouse RIP-YFP plasmid construction in serum-free medium using Lipofectamine

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2000 Reagents.We tested pancreatic specific gene expression and characterized these ESC-derived pancreatic endocrine cells.Most of these insulin-secreting cells co-expressed many of the phenotypic markers characteristic ofβcells such as insulinl

insulin2

Isletl

MafA

insulinoma-associated antigen 1（IA1） and so on

indicating a similar gene expression pattern to adult islet p cells in vivo.Characterization of this population revealed that it consisted predominantly of pancreatic endocrine cells that were able to undergo pancreatic specification under the appropriate conditions.We also demonstrated that zinc supplementation mediated up-regulation of insulin-secreting cells as an effective inducer promoted the development of ESC-derived diabetes therapy.In conclusion

this work not only established an efficient pancreatic differentiation strategy from ESCs to pancreatic endocrine lineage in vitro

but also leaded to the development of new strategies to derive transplantable islet-replacementβcells from embryonic stem cells for the future applications of a stem cell based therapy of diabetes.