Pancreatic islet cell development and regeneration.
Pancreatic islet cell development and regeneration.
复制标题
DOI：
10.1097/med.0000000000000174
复制
发表时间：
2015-08
期刊：
影响因子：
--
通讯作者：
Sussel L
中科院分区：
文献类型：
--
作者：
Romer AI;Sussel L
本文将讨论最近的进展，了解小鼠和人类胰岛细胞的发展，新的概念相关的β细胞功能障碍和改善方法补充β细胞治疗糖尿病。使用模型系统已经获得了关于胰岛发育和功能的相当多的知识，随后在人体组织中进行了验证。最近，一些啮齿类动物的研究表明，分化的成年胰岛细胞保持显着的可塑性，并可以转换为其他类型的胰岛细胞通过扰乱他们的转录因子谱。此外，在从干细胞群体产生β样细胞方面已经取得了显著进展。因此，通过原位转化非β细胞群体或通过人多能干细胞的定向分化产生功能成熟的β细胞可以代表补充糖尿病患者中的β细胞的新机制。小鼠和人胰腺发育、胰岛生理学和糖尿病病因学之间的总体保守性鼓励将新型β细胞替代疗法转化为人类。进一步阐明指导胰岛细胞再生、可塑性和功能的分子机制可以改善和扩展治疗糖尿病的β细胞替代策略。
This review will discuss recent advances in understanding mouse and human pancreatic islet cell development, novel concepts related to β cell dysfunction and improved approaches for replenishing β cells to treat diabetes. Considerable knowledge about pancreatic islet development and function has been gained using model systems with subsequent validation in human tissues. Recently, several rodent studies have revealed that differentiated adult islet cells retain remarkable plasticity and can be converted to other islet cell types by perturbing their transcription factor profiles. Furthermore, significant advances have been made in the generation of β-like cells from stem cell populations. Therefore, the generation of functionally mature β cells by the in situ conversion of non-β cell populations or by the directed differentiation of human pluripotent stem cells could represent novel mechanisms for replenishing β cells in diabetic patients. The overall conservation between mouse and human pancreatic development, islet physiology and etiology of diabetes encourages the translation of novel β cell replacement therapies to humans. Further deciphering the molecular mechanisms that direct islet cell regeneration, plasticity and function could improve and expand the β cell replacement strategies for treating diabetes.