Facilitating islet transplantation using a three-step approach with mesenchymal stem cells, encapsulation, and pulsed focused ultrasound
| Autor: | Arsenii V. Telichko, Jeremy J. Dahl, Jing Wang, Utkan Demirci, Fengyang Zheng, Tanchen Ren, Mehdi Razavi, Avnesh S. Thakor |
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| Rok vydání: | 2020 |
| Předmět: |
endocrine system
endocrine system diseases Islets transplantation medicine.medical_treatment Islets of Langerhans Transplantation Pulsed focused ultrasound Medicine (miscellaneous) Adipose tissue Mesenchymal Stem Cell Transplantation Biochemistry Genetics and Molecular Biology (miscellaneous) Diabetes Mellitus Experimental lcsh:Biochemistry Islets of Langerhans Mice medicine Animals lcsh:QD415-436 lcsh:R5-920 geography Islet cell transplantation geography.geographical_feature_category Chemistry Research Diabetes Mesenchymal stem cell Capsule Cell Biology Islet In vitro Cell biology Transplantation Mesenchymal stem cells Molecular Medicine Encapsulation Stem cell lcsh:Medicine (General) |
| Zdroj: | Stem Cell Research & Therapy, Vol 11, Iss 1, Pp 1-17 (2020) Stem Cell Research & Therapy |
| ISSN: | 1757-6512 |
| DOI: | 10.1186/s13287-020-01897-z |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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