Gastroenterology Division, Department of Medicine.
Department of Cell and Developmental Biology, and.
JCI Insight. 2019 Nov 1;4(21):124644. doi: 10.1172/jci.insight.124644.
Islet transplantation is an effective therapy for achieving and maintaining normoglycemia in patients with type 1 diabetes mellitus. However, the supply of transplantable human islets is limited. Upon removal from the pancreas, islets rapidly disintegrate and lose function, resulting in a short interval for studies of islet biology and pretransplantation assessment. Here, we developed a biomimetic platform that can sustain human islet physiology for a prolonged period ex vivo. Our approach involved the creation of a multichannel perifusion system to monitor dynamic insulin secretion and intracellular calcium flux simultaneously, enabling the systematic evaluation of glucose-stimulated insulin secretion under multiple conditions. Using this tool, we developed a nanofibrillar cellulose hydrogel-based islet-preserving platform (iPreP) that can preserve islet viability, morphology, and function for nearly 12 weeks ex vivo, and with the ability to ameliorate glucose levels upon transplantation into diabetic hosts. Our platform has potential applications in the prolonged maintenance of human islets, providing an expanded time window for pretransplantation assessment and islet studies.
胰岛移植是实现和维持 1 型糖尿病患者血糖正常的有效治疗方法。然而,可移植的人类胰岛的供应是有限的。从胰腺中取出后,胰岛迅速解体并丧失功能,导致胰岛生物学和移植前评估的研究时间间隔很短。在这里,我们开发了一种仿生平台,可以在体外长时间维持人类胰岛的生理学功能。我们的方法包括创建一个多通道灌注系统,同时监测动态胰岛素分泌和细胞内钙流,从而能够在多种条件下系统地评估葡萄糖刺激的胰岛素分泌。使用这种工具,我们开发了一种基于纳米纤维纤维素水凝胶的胰岛保存平台(iPreP),可以在体外保存胰岛的活力、形态和功能近 12 周,并且在移植到糖尿病宿主后能够改善血糖水平。我们的平台具有在延长时间内维持人类胰岛的潜力,为移植前评估和胰岛研究提供了更大的时间窗口。