Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound.
Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound.
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DOI：
10.1186/s13287-020-01897-z
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发表时间：
2020-09-18
影响因子：
7.5
通讯作者：
Thakor AS
中科院分区：
文献类型：
--
作者：
Razavi M;Ren T;Zheng F;Telichko A;Wang J;Dahl JJ;Demirci U;Thakor AS
本研究的目的是检查三步法的效果，该方法利用脂肪组织来源的间充质干细胞（AD-MSCs），包封和脉冲聚焦超声（pFUS）的应用，以帮助移植胰岛的植入和功能。在步骤1中，将胰岛与AD-MSC共培养以在胰岛上形成AD-MSC的涂层：在此，AD-MSC对胰岛具有细胞保护作用;在步骤2中，使用同轴气流方法将涂覆有AD-MSC的胰岛共形地包封在海藻酸盐薄层中：在此，该胶囊使AD-MSC能够紧密接近胰岛;在步骤3中，用pFUS处理包被有AD-MSC的包封的胰岛：在此，pFUS增强胰岛分泌胰岛素以及刺激AD-MSC的细胞保护作用。我们的方法被证明可以防止胰岛死亡并在体外保持胰岛功能。当将175个用AD-MSC包被的同源包封的胰岛移植到糖尿病小鼠的肾被膜下，然后每3天用pFUS治疗一次直到移植后第12天时，我们看到胰岛功能的显著改善，糖尿病动物在我们的研究过程中重新建立血糖控制（即，30天）。此外，我们的方法能够通过促进胰岛血管重建和减少炎症来增强胰岛植入。这项研究表明，我们的临床可翻译的三步法能够改善移植胰岛的功能和活力。
The aim of this study was to examine the effect of a three-step approach that utilizes the application of adipose tissue-derived mesenchymal stem cells (AD-MSCs), encapsulation, and pulsed focused ultrasound (pFUS) to help the engraftment and function of transplanted islets. In step 1, islets were co-cultured with AD-MSCs to form a coating of AD-MSCs on islets: here, AD-MSCs had a cytoprotective effect on islets; in step 2, islets coated with AD-MSCs were conformally encapsulated in a thin layer of alginate using a co-axial air-flow method: here, the capsule enabled AD-MSCs to be in close proximity to islets; in step 3, encapsulated islets coated with AD-MSCs were treated with pFUS: here, pFUS enhanced the secretion of insulin from islets as well as stimulated the cytoprotective effect of AD-MSCs. Our approach was shown to prevent islet death and preserve islet functionality in vitro. When 175 syngeneic encapsulated islets coated with AD-MSCs were transplanted beneath the kidney capsule of diabetic mice, and then followed every 3 days with pFUS treatment until day 12 post-transplantation, we saw a significant improvement in islet function with diabetic animals re-establishing glycemic control over the course of our study (i.e., 30 days). In addition, our approach was able to enhance islet engraftment by facilitating their revascularization and reducing inflammation. This study demonstrates that our clinically translatable three-step approach is able to improve the function and viability of transplanted islets.
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