Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed fo
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(2020) 11:405
RESEARCH
Open Access
Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound Mehdi Razavi1,2,3, Tanchen Ren4, Fengyang Zheng1, Arsenii Telichko5, Jing Wang1, Jeremy J. Dahl5, Utkan Demirci4 and Avnesh S. Thakor1*
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. Keywords: Islets transplantation, Mesenchymal stem cells, Encapsulation, Pulsed focused ultrasound, Diabetes
* Correspondence: [email protected] 1 Department of Radiology, Interventional Regenerative Medicine and Imaging Laboratory, Stanford University School of Medicine, 3155 Porter Drive, Palo Alto, CA 94304, USA Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyr
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