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使用具有双重功能的 MRI 可见和可回收微胶囊从糖尿病小鼠中磁性回收包封的胰岛细胞移植体。

Magnetic Retrieval of Encapsulated Beta Cell Transplants from Diabetic Mice Using Dual-Function MRI Visible and Retrievable Microcapsules.

机构信息

David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, 500 Main Street, Cambridge, MA, 02139, USA.

Department of Anesthesiology, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.

出版信息

Adv Mater. 2020 Apr;32(16):e1904502. doi: 10.1002/adma.201904502. Epub 2020 Mar 5.

Abstract

Encapsulated beta cell transplantation offers a potential cure for a subset of diabetic patients. Once transplanted, beta cell grafts can help to restore glycemic control; however, locating and retrieving cells in the event of graft failure may pose a surgical challenge. Here, a dual-function nanoparticle-loaded hydrogel microcapsule is developed that enables graft retrieval under an applied magnetic field. Additionally, this system facilitates graft localization via magnetic resonance imaging (MRI), and graft isolation from the immune system. Iron oxide nanoparticles encapsulated within alginate hydrogel capsules containing viable islets are transplanted and the in vitro and in vivo retrieval of capsules containing nanoparticles functionalized with various ligands are compared. Capsules containing islets co-encapsulated with COOH-coated nanoparticles restore normal glycemia in immunocompetent diabetic mice for at least 6 weeks, can be visualized using MRI, and are retrievable in a magnetic field. Application of a magnetic field for 90 s via a magnetically assisted retrieval device facilitates rapid retrieval of up to 94% (±3.1%) of the transplant volume 24 h after surgical implantation. This strategy aids monitoring of cell-capsule locations in vivo, facilitates graft removal at the end of the transplant lifetime, and may be applicable to many encapsulated cell transplant systems.

摘要

包被β细胞移植为一部分糖尿病患者提供了一种潜在的治疗方法。一旦移植,β细胞移植物有助于恢复血糖控制;然而,在移植物失功的情况下定位和取回细胞可能会带来手术挑战。在这里,开发了一种具有双重功能的载纳米粒子水凝胶微胶囊,可在施加磁场的情况下进行移植物取回。此外,该系统通过磁共振成像 (MRI) 促进移植物定位,并将移植物与免疫系统隔离。将包封在含有存活胰岛的藻酸盐水凝胶胶囊中的氧化铁纳米粒子移植,并比较了用各种配体功能化的纳米粒子对含有纳米粒子的胶囊的体外和体内回收。与 COOH 涂层纳米粒子共包封的胰岛的胶囊在免疫功能正常的糖尿病小鼠中至少可恢复正常血糖水平 6 周,可通过 MRI 可视化,并可在磁场中回收。通过磁性辅助回收装置施加磁场 90 秒可促进在手术植入后 24 小时内快速回收高达 94%(±3.1%)的移植体积。该策略有助于监测体内细胞-胶囊位置,便于在移植寿命结束时去除移植物,并且可能适用于许多包被细胞移植系统。

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