Facilitating Islet Transplantation Using a Three-step Approach with Mesenchymal Stem Cells, Encapsulation, and Pulsed Focused Ultrasound

Journal: Stem Cell Research & Therapy
Authors: Mehdi Razavi, Tanchen Ren, Fengyang Zheng, Arsenii Telichko, Jing Wang, Jeremy J Dahl, Utkan Demirci, Avnesh S Thakor

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusions: This study demonstrates that our clinically translatable three-step approach is able to improve the function and viability of transplanted islets.

Read more: https://doi.org/10.1186/s13287-020-01897-z

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