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磁共振引导下磁胶囊对胰岛细胞进行免疫保护的实时靶向递送与成像

Magnetic resonance-guided, real-time targeted delivery and imaging of magnetocapsules immunoprotecting pancreatic islet cells.

作者信息

Barnett Brad P, Arepally Aravind, Karmarkar Parag V, Qian Di, Gilson Wesley D, Walczak Piotr, Howland Valerie, Lawler Leo, Lauzon Cal, Stuber Matthias, Kraitchman Dara L, Bulte Jeff W M

机构信息

Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins Medical Institutes, Blalock 644, 600 North Wolfe Street, Baltimore, Maryland 21212, USA.

出版信息

Nat Med. 2007 Aug;13(8):986-91. doi: 10.1038/nm1581. Epub 2007 Jul 29.

Abstract

In type I diabetes mellitus, islet transplantation provides a moment-to-moment fine regulation of insulin. Success rates vary widely, however, necessitating suitable methods to monitor islet delivery, engraftment and survival. Here magnetic resonance-trackable magnetocapsules have been used simultaneously to immunoprotect pancreatic beta-cells and to monitor, non-invasively in real-time, hepatic delivery and engraftment by magnetic resonance imaging (MRI). Magnetocapsules were detected as single capsules with an altered magnetic resonance appearance on capsule rupture. Magnetocapsules were functional in vivo because mouse beta-cells restored normal glycemia in streptozotocin-induced diabetic mice and human islets induced sustained C-peptide levels in swine. In this large-animal model, magnetocapsules could be precisely targeted for infusion by using magnetic resonance fluoroscopy, whereas MRI facilitated monitoring of liver engraftment over time. These findings are directly applicable to ongoing improvements in islet cell transplantation for human diabetes, particularly because our magnetocapsules comprise clinically applicable materials.

摘要

在I型糖尿病中,胰岛移植可实现胰岛素的即时精细调节。然而,成功率差异很大,因此需要合适的方法来监测胰岛的输送、植入和存活情况。在此,可通过磁共振追踪的磁胶囊被同时用于免疫保护胰腺β细胞,并通过磁共振成像(MRI)实时、无创地监测肝脏中的输送和植入情况。磁胶囊在破裂时会以磁共振外观改变的形式被检测为单个胶囊。磁胶囊在体内具有功能,因为小鼠β细胞可使链脲佐菌素诱导的糖尿病小鼠恢复正常血糖水平,而人胰岛可使猪体内的C肽水平持续升高。在这个大型动物模型中,通过磁共振荧光透视法可将磁胶囊精确靶向注入,而MRI有助于长期监测肝脏植入情况。这些发现可直接应用于目前人类糖尿病胰岛细胞移植的改进,特别是因为我们的磁胶囊包含临床适用材料。

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