MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys.
MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys.
复制标题
猴子自体胰腺祖细胞来源的胰岛素产生细胞的 MRI 追踪
DOI：
10.1038/s41598-017-02775-0
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发表时间：
2017-05-31
影响因子：
4.6
通讯作者：
Zhang YA
中科院分区：
文献类型：
--
作者：
Zou C;Lu Y;Teng X;Wang S;Sun X;Huang F;Shu G;Huang X;Guo H;Chen Z;Zhang J;Zhang YA
来自患者自身干细胞的胰岛素产生细胞（IPC）为糖尿病患者的自体移植提供了巨大的潜力。然而，移植细胞的有限存活仍然是该策略应用的瓶颈。本研究旨在研究基于纳米颗粒的磁共振（MR）跟踪是否可用于在糖尿病猴模型中以灵敏和及时的方式检测移植干细胞衍生的IPC的丢失。从糖尿病猴中分离胰腺祖细胞（PPC），并用超顺磁性氧化铁纳米颗粒（SPION）标记。SPION标记细胞在MRI上呈低信号。标记程序不影响PPC的活力或IPC分化。重要的是，SPION标记的IPC在肝脏MRI上引起的低信号总面积在自体移植后C肽水平下降之前下降。组织学分析显示，在移植后一年，移植物和许多存活的胰岛素和普鲁士蓝阳性细胞簇在肝切片上没有检测到免疫反应。总的来说，这项研究表明，SPIO纳米粒子可用于标记干细胞的非侵入性，敏感，纵向监测干细胞衍生的IPC在大型动物模型中使用传统的MR成像仪。
Insulin-producing cells (IPCs) derived from a patient’s own stem cells offer great potential for autologous transplantation in diabetic patients. However, the limited survival of engrafted cells remains a bottleneck in the application of this strategy. The present study aimed to investigate whether nanoparticle-based magnetic resonance (MR) tracking can be used to detect the loss of grafted stem cell-derived IPCs in a sensitive and timely manner in a diabetic monkey model. Pancreatic progenitor cells (PPCs) were isolated from diabetic monkeys and labeled with superparamagnetic iron oxide nanoparticles (SPIONs). The SPION-labeled cells presented as hypointense signals on MR imaging (MRI). The labeling procedure did not affect the viability or IPC differentiation of PPCs. Importantly, the total area of the hypointense signal caused by SPION-labeled IPCs on liver MRI decreased before the decline in C-peptide levels after autotransplantation. Histological analysis revealed no detectable immune response to the grafts and many surviving insulin- and Prussian blue-positive cell clusters on liver sections at one year post-transplantation. Collectively, this study demonstrates that SPIO nanoparticles can be used to label stem cells for noninvasive, sensitive, longitudinal monitoring of stem cell-derived IPCs in large animal models using a conventional MR imager.