Australian Research Council Centre of Excellence for Nanoscale BioPhotonics, Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW 2033, Australia.
Garvan Institute of Medical Research, Faculty of Medicine, St Vincent's Clinical School, University of New South Wales, Sydney, NSW 2052, Australia.
Cells. 2023 Sep 19;12(18):2302. doi: 10.3390/cells12182302.
Islets prepared for transplantation into type 1 diabetes patients are exposed to compromising intrinsic and extrinsic factors that contribute to early graft failure, necessitating repeated islet infusions for clinical insulin independence. A lack of reliable pre-transplant measures to determine islet viability severely limits the success of islet transplantation and will limit future beta cell replacement strategies. We applied hyperspectral fluorescent microscopy to determine whether we could non-invasively detect islet damage induced by oxidative stress, hypoxia, cytokine injury, and warm ischaemia, and so predict transplant outcomes in a mouse model. In assessing islet spectral signals for NAD(P)H, flavins, collagen-I, and cytochrome-C in intact islets, we distinguished islets compromised by oxidative stress (ROS) (AUC = 1.00), hypoxia (AUC = 0.69), cytokine exposure (AUC = 0.94), and warm ischaemia (AUC = 0.94) compared to islets harvested from pristine anaesthetised heart-beating mouse donors. Significantly, with unsupervised assessment we defined an autofluorescent score for ischaemic islets that accurately predicted the restoration of glucose control in diabetic recipients following transplantation. Similar results were obtained for islet single cell suspensions, suggesting translational utility in the context of emerging beta cell replacement strategies. These data show that the pre-transplant hyperspectral imaging of islet autofluorescence has promise for predicting islet viability and transplant success.
准备用于移植到 1 型糖尿病患者的胰岛会受到内在和外在因素的影响,这些因素会导致早期移植物失功,需要反复输注胰岛以实现临床胰岛素独立性。缺乏可靠的移植前措施来确定胰岛活力严重限制了胰岛移植的成功,并将限制未来的β细胞替代策略。我们应用高光谱荧光显微镜来确定我们是否可以非侵入性地检测到氧化应激、缺氧、细胞因子损伤和热缺血引起的胰岛损伤,并因此预测小鼠模型中的移植结果。在评估完整胰岛中 NAD(P)H、黄素、I 型胶原和细胞色素 C 的胰岛光谱信号时,我们将受到氧化应激(ROS)(AUC = 1.00)、缺氧(AUC = 0.69)、细胞因子暴露(AUC = 0.94)和热缺血(AUC = 0.94)影响的胰岛与从原始麻醉心脏跳动供体中收获的胰岛区分开来。重要的是,通过无监督评估,我们为缺血胰岛定义了一个自发荧光评分,该评分可以准确预测移植后糖尿病受者血糖控制的恢复。胰岛单细胞悬液也得到了类似的结果,这表明在新兴的β细胞替代策略背景下具有转化应用的潜力。这些数据表明,胰岛自发荧光的移植前高光谱成像具有预测胰岛活力和移植成功的潜力。