Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound

Stem Cell Research & Therapy

Tanchen Ren¹  Utkan Demirci¹  Arsenii Telichko²  Jeremy J. Dahl²  Jing Wang³  Fengyang Zheng³  Avnesh S. Thakor³  Mehdi Razavi⁴ 

[1] Department of Radiology, Bio-Acoustic MEMS in Medicine Laboratory (BAMM), Stanford University School of Medicine, 94304, Palo Alto, CA, USA;Department of Radiology, Dahl Ultrasound Laboratory, Stanford University School of Medicine, 94304, Palo Alto, CA, USA;Department of Radiology, Interventional Regenerative Medicine and Imaging Laboratory, Stanford University School of Medicine, 3155 Porter Drive, 94304, Palo Alto, CA, USA;Department of Radiology, Interventional Regenerative Medicine and Imaging Laboratory, Stanford University School of Medicine, 3155 Porter Drive, 94304, Palo Alto, CA, USA;Biionix™ (Bionic Materials, Implants & Interfaces) Cluster, Department of Internal Medicine, College of Medicine, University of Central Florida, 32827, Orlando, FL, USA;Department of Materials Science and Engineering, University of Central Florida, 32816, Orlando, FL, USA;

关键词: Islets transplantation;    Mesenchymal stem cells;    Encapsulation;    Pulsed focused ultrasound;    Diabetes;   

DOI  :  10.1186/s13287-020-01897-z

来源: Springer

【 摘 要 】

BackgroundThe 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.MethodsIn 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.ResultsOur 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.ConclusionsThis study demonstrates that our clinically translatable three-step approach is able to improve the function and viability of transplanted islets.

【 授权许可】

CC BY