Disease Biophysics Group, Wyss Institute for Biologically Inspired Engineering, Harvard John A. Paulson School of Engineering and Applied Sciences, Harvard University, Cambridge, MA.
Harvard Department of Stem Cell and Regenerative Biology, Cambridge, MA.
Diabetes. 2021 Feb;70(2):347-363. doi: 10.2337/db20-0297.
Diabetes is a disease of insulin insufficiency, requiring many to rely on exogenous insulin with constant monitoring to avoid a fatal outcome. Islet transplantation is a recent therapy that can provide insulin independence, but the procedure is still limited by both the availability of human islets and reliable tests to assess their function. While stem cell technologies are poised to fill the shortage of transplantable cells, better methods are still needed for predicting transplantation outcome. To ensure islet quality, we propose that the next generation of islet potency tests should be biomimetic systems that match glucose stimulation dynamics and cell microenvironmental preferences and rapidly assess conditional and continuous insulin secretion with minimal manual handing. Here, we review the current approaches for islet potency testing and outline technologies and methods that can be used to arrive at a more predictive potency test that tracks islet secretory capacity in a relevant context. With the development of potency tests that can report on islet secretion dynamics in a context relevant to their intended function, islet transplantation can expand into a more widely accessible and reliable treatment option for individuals with diabetes.
糖尿病是一种胰岛素不足的疾病，许多患者需要依靠外源性胰岛素，并进行持续监测，以避免致命的后果。胰岛移植是一种最近的治疗方法，可以提供胰岛素的独立性，但该过程仍然受到人胰岛的可用性和可靠的功能评估测试的限制。虽然干细胞技术有望填补可移植细胞的短缺，但仍需要更好的方法来预测移植结果。为了确保胰岛的质量，我们建议下一代胰岛效力测试应该是仿生系统，以匹配葡萄糖刺激动力学和细胞微环境偏好，并快速评估条件和连续胰岛素分泌，尽量减少手动操作。在这里，我们回顾了目前的胰岛效力测试方法，并概述了可以用来建立更具预测性的效力测试的技术和方法，该测试可以在相关背景下跟踪胰岛的分泌能力。随着能够报告与预期功能相关的胰岛分泌动力学的效力测试的发展，胰岛移植可以扩展成为一种更广泛适用和可靠的糖尿病治疗选择。
