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MRI 示踪自体胰腺祖细胞衍生的胰岛素分泌细胞在猴体内的变化。

MRI tracking of autologous pancreatic progenitor-derived insulin-producing cells in monkeys.

机构信息

Center for Translational Medicine, Guangxi Medical University, Guangxi, P.R. China.

Cell Therapy Center, Xuanwu Hospital, Capital Medical University, Beijing, P.R. China.

出版信息

Sci Rep. 2017 May 31;7(1):2505. doi: 10.1038/s41598-017-02775-0.

DOI:10.1038/s41598-017-02775-0
PMID:28566744
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5451407/
Abstract

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.

摘要

由患者自身干细胞衍生的胰岛素产生细胞 (IPCs) 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一个瓶颈。本研究旨在探讨基于纳米颗粒的磁共振 (MR) 追踪是否可用于敏感且及时地检测糖尿病猴模型中移植干细胞衍生的 IPC 的丢失。从糖尿病猴中分离出胰腺祖细胞 (PPCs) 并进行超顺磁氧化铁纳米颗粒 (SPION) 标记。SPION 标记的细胞在磁共振成像 (MRI) 上呈现为低信号。标记过程不影响 PPCs 的活力或 IPC 分化。重要的是,在自体移植后 C 肽水平下降之前,肝 MRI 上由 SPION 标记的 IPCs 引起的低信号总面积会减小。组织学分析显示,在移植后一年的肝切片上,没有检测到对移植物的免疫反应,并且存在许多存活的胰岛素和普鲁士蓝阳性细胞簇。总之,这项研究表明,SPIO 纳米颗粒可用于标记干细胞,以便使用常规 MR 成像仪对大动物模型中的干细胞衍生的 IPC 进行非侵入性、敏感、纵向监测。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/38595947d785/41598_2017_2775_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/0d9b7c3bd6f9/41598_2017_2775_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/daad8df788ef/41598_2017_2775_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/66b250af67b3/41598_2017_2775_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/11548f06deb5/41598_2017_2775_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/38595947d785/41598_2017_2775_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/0d9b7c3bd6f9/41598_2017_2775_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/daad8df788ef/41598_2017_2775_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/66b250af67b3/41598_2017_2775_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/11548f06deb5/41598_2017_2775_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6149/5451407/38595947d785/41598_2017_2775_Fig5_HTML.jpg

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本文引用的文献

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Autologous iPSC-derived dopamine neuron transplantation in a nonhuman primate Parkinson's disease model.在非人灵长类帕金森病模型中进行自体诱导多能干细胞衍生的多巴胺神经元移植。
Cell Discov. 2015 May 26;1:15012. doi: 10.1038/celldisc.2015.12. eCollection 2015.
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The state of the art of islet transplantation and cell therapy in type 1 diabetes.1型糖尿病胰岛移植与细胞治疗的现状
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Long-term glycemic control using polymer-encapsulated human stem cell-derived beta cells in immune-competent mice.
在具有免疫活性的小鼠中使用聚合物封装的人干细胞衍生的β细胞进行长期血糖控制。
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Long-Term Follow-Up of the Edmonton Protocol of Islet Transplantation in the United States.美国胰岛移植 Edmonton 方案的长期随访结果。
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