Noguchi Hirofumi
Regenerative Research Islet Transplant Program, Baylor Research Institute, 1400 8th Avenue, Fort Worth, TX 76104, USA.
Curr Diabetes Rev. 2010 May;6(3):184-90. doi: 10.2174/157339910791162934.
Diabetes remains a major burden. More than 200 million people are affected worldwide, which represents 6% of the population. The success achieved over the last decade with islet transplantation suggests that diabetes can be cured by the replenishment of deficient beta cells. These observations are proof-of-concept and have intensified interest in treating diabetes not only by cell transplantation but also by stem cells. Regeneration of beta cells from stem and progenitor cells is an attractive method to restore islet cell mass. Pancreatic stem/progenitor cells have been identified, and the formation of new beta cells from pancreatic duct, acinar and liver cells is an active area of investigation. Protocols for the in vitro differentiation of embryonic stem (ES) cells based on normal developmental processes have generated beta-like cells that produce high levels of insulin, even though at low efficiency and without full responsiveness to extracellular levels of glucose. Induced pluripotent stem (iPS) cells can also yield insulin-producing cells following similar approaches. Some agents including glucagon-like peptide-1/exendin-4 can stimulate the regeneration of beta cells in vivo as well as in vitro. Overexpression of embryonic transcription factors in stem cells could efficiently induce their differentiation into insulin-expressing cells. Recent progress in the search for new sources of beta cells has opened up several possibilities for the development of new treatments for diabetes.
糖尿病仍然是一项重大负担。全球有超过2亿人受其影响，占总人口的6%。过去十年胰岛移植所取得的成功表明，补充不足的β细胞可以治愈糖尿病。这些观察结果是概念验证，不仅增强了人们对通过细胞移植治疗糖尿病的兴趣，也增强了对通过干细胞治疗糖尿病的兴趣。由干细胞和祖细胞再生β细胞是恢复胰岛细胞数量的一种有吸引力的方法。胰腺干细胞/祖细胞已被识别出来，从胰腺导管、腺泡和肝细胞形成新的β细胞是一个活跃的研究领域。基于正常发育过程的胚胎干细胞体外分化方案已产生了能产生高水平胰岛素的β样细胞，尽管效率较低且对细胞外葡萄糖水平没有完全反应。诱导多能干细胞（iPS细胞）采用类似方法也能产生胰岛素分泌细胞。一些药物，包括胰高血糖素样肽-1/艾塞那肽-4，在体内和体外都能刺激β细胞的再生。干细胞中胚胎转录因子的过表达能有效诱导它们分化为胰岛素表达细胞。寻找β细胞新来源的最新进展为开发糖尿病新疗法开辟了多种可能性。
