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Differentiation of mouse embryonic stem cells into insulin-secreting cells in vitro 被引量:1

Differentiation of mouse embryonic stem cells into insulin-secreting cells in vitro
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摘要 包括房间代替策略,再生药可以在与减少的小岛房间质量被联系的类型 1 糖尿病的治疗有一个重要角色。迄今为止,重要进步在从 pluripotent 老鼠产生胰岛素秘密房间被成为了胚胎的干细胞(转换字符) 。这研究的目的探索调整转换字符的区别进胰腺的内分泌的房间的潜力能够综合包括在合适的条件下面的胰岛素, glucagon, somatostatin 和胰腺的多肽的胰腺的荷尔蒙。无差别的 ES 房间线稳定地,有在没有浆液的媒介的老鼠 RIP-YFP plasmid 建设的 transfected 使用 Lipofectamine?2000 试剂。我们测试了胰腺的特定的基因表示并且描绘了这些导出转换字符的胰腺的内分泌的房间。大多数这些胰岛素秘密房间共同表示许多象 insulin1 那样的房间的 phenotypic 标记特征, insulin2, Islet1, MafA,联系 insulinoma 的抗原 1 (IA1 ) 等等,在 vivo 显示一个类似的基因表示模式到成年小岛房间。这张人口的描述表明它由能在适当条件下面经历胰腺的说明的胰腺的内分泌的房间主要组成了。我们也表明了那锌补充有效 inducer 支持了导出转换字符的糖尿病的发展的胰岛素秘密房间的调停的起来规定治疗。在结论,这个工作不仅在 vitro 从转换字符建立了有效胰腺的区别策略到胰腺的内分泌的系,而且导致了新策略的开发为一个干细胞的未来应用程序从胚胎的干细胞导出可移植的小岛代替房间糖尿病的基于的治疗。 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-secreting 13 cells 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 LipofectamineTM 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 of 13 cells such as insulinl, insulin2, Isletl, MafA, insulinoma-associated antigen 1 (IA1) and so on, indicating a similar gene expression pattern to adult islet 13 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-replacement 13 cells from embryonic stem cells for the future applications of a stem cell based therapy of diabetes.
出处 《Journal of Medical Colleges of PLA(China)》 CAS 2011年第1期1-12,共12页 中国人民解放军军医大学学报(英文版)
关键词 内分泌细胞 小鼠胚胎 细胞分化 胰岛素 体外 胚胎干细胞系 基因表达模式 内分泌激素 Embryonic stem cells Pancreatic differentiation Insulin-secreting cells Transcription factors Zinc
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