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MICROFLUIDICS FOR LIVE-CELL IMAGING PANCREATIC ISLETS OF LANGERHANS FOR HUMAN TRANSPLANT

机译:Langerhans的Langerhans活细胞成像胰岛的微流体

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Since the introduction of the Edmonton Protocol in 2000, islet transplantation has been emerging as promising therapy for Type I diabetes mellitus (T1DM) and currently is the only therapy that can achieve glycemic control without the need for exogenous insulin. Transplanting islet cells has several advantages over transplanting a whole pancreas in that it involves only a minor surgical procedure with low morbidity and mortality, and at a significantly lower cost. However, an obstacle to realizing this goal is a lack of an islet potency index as required by the U.S. Food and Drug Administration (FDA) biologics licensing, as well as a more complete understanding of the physiological mechanisms governing islet and β-cell physiology. Recently, the University of Illinois at Chicago (UIC) has developed a microfluidic platform that can mimic in vivo islet microenvironments through precise and dynamic control of perifusing culture media and oxygen culture levels; all while measuring functionally relevant factors including intracellular calcium levels, mitochondrial potentials, and insulin secretion. By developing an understanding of the physiology and pathophysiology of islets we can more effectively develop strategies that reduce metabolic stress and promote optimization in order to achieve improved success of islet transplantation and open new clinical avenues. The presentation begins by introducing key issues in the field of pancreatic islet transplantation as a clinical therapy for T1DM. This is followed by brief review various technologies that have been developed to study islet cells. The presentation then describes the design, application, and evolution of UIC's microfluidic-based multimodal islet perifusion and live-cell imaging system for the study of pancreatic islet and β-cell physiology. The article then concludes presenting initial findings from studies seeking to develop an islet potency test.
机译:自2000年埃德蒙顿协议引入以来,胰岛移植已成为I型糖尿病(T1DM)的承诺治疗,目前是唯一可以实现血糖控制而不需要外源性胰岛素的治疗。移植胰岛细胞在移植整个胰腺中具有若干优点,因为它仅涉及发病率和死亡率低的次要外科手术,并且成本明显更低。然而,实现这一目标的障碍是根据美国食品和药物管理局(FDA)生物学许可所要求的缺乏胰岛效力指数,以及对治疗胰岛和β细胞生理学的生理机制更完全了解。近日,伊利诺伊大学芝加哥(UIC)开发了一种微流体平台,可以通过精确和动态控制体内胰岛微环境模仿围绕培养介质和氧培养水平;虽然测量功能相关的因素,包括细胞内钙水平,线粒体电位和胰岛素分泌。通过制定对胰岛的生理学和病理生理学的理解,我们可以更有效地发展减少代谢应激的策略,并促进优化,以实现胰岛移植的提高成功,开放新的临床途径。介绍首先在胰岛移植领域引入作为T1DM的临床治疗的关键问题。随后是简要介绍开发的各种技术,以研究胰岛细胞。然后,介绍描述了UIC的基于微流体的多模式胰岛漂流和用于研究胰岛和β细胞生理学的活细胞成像系统的设计,应用和演化。然后,该文章结束了寻求发展胰岛效力试验的研究初始发现。

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