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.

中文翻译：

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使用间充质干细胞、封装和脉冲聚焦超声三步法促进胰岛移植。


本研究的目的是检查三步法的效果，该法利用脂肪组织源性间充质干细胞 (AD-MSC)、封装和脉冲聚焦超声 (pFUS) 的应用来帮助植入和功能移植的胰岛。步骤1，将胰岛与AD-MSC共培养，在胰岛上形成AD-MSC的涂层：此时，AD-MSC对胰岛具有细胞保护作用；步骤2中，使用同轴气流法将涂有AD-MSC的胰岛保形封装在一层薄薄的藻酸盐中：此时，胶囊使AD-MSC能够非常接近胰岛；在步骤3中，用pFUS处理包被有AD-MSC的封装胰岛：在这里，pFUS增强了胰岛的胰岛素分泌，并刺激了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留胰岛功能。当将 175 个涂有 AD-MSC 的同系封装胰岛移植到糖尿病小鼠的肾被膜下方，然后每 3 天进行一次 pFUS 治疗直至移植后第 12 天时，我们发现糖尿病小鼠的胰岛功能显着改善，并重新建立了功能我们研究过程中（即 30 天）的血糖控制。此外，我们的方法能够通过促进血运重建和减少炎症来增强胰岛移植。这项研究表明，我们的临床可转化三步方法能够改善移植胰岛的功能和活力。