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Permanent link (DOI): https://doi.org/10.7939/R36T0H926

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Co-transplantation of mesenchymal stem cells with islet grafts Open Access

Descriptions

Other title
Subject/Keyword
neonatal porcine islets
Diabetes mellitus type I
mesenchymal stem cells
islet transplantation
Type of item
Thesis
Degree grantor
University of Alberta
Author or creator
Hayward, Julie A
Supervisor and department
Korbutt, Gregory (Surgery)
Examining committee member and department
Postovit, Lynne (Oncology)
Korbutt, Gregory (Surgery)
Churchill, Tom (Surgery)
Adesida, Adetola (Surgery)
Department
Department of Surgery
Specialization

Date accepted
2017-08-02T10:10:16Z
Graduation date
2017-11:Fall 2017
Degree
Master of Science
Degree level
Master's
Abstract
Mesenchymal stem cells (MSCs) have immuno-regulatory, anti-inflammatory, and pro-angiogenic properties through the secretion of a myriad of trophic factors, and have been shown to have a beneficial effect on graft function. In this thesis we investigated whether MSCs’ have an effect on neonatal porcine islets (NPIs) in vitro and in vivo. For the in vitro studies, NPIs were cultured with or without MSCs for 48 hours and a glucose stimulated insulin secretion (GSIS) assay was administered. NPIs cultured with MSCs had higher cellular insulin content and improved GSIS. For in vivo studies, NPIs cultured with or without MSC were transplanted under the kidney capsule of streptozotocin-induced diabetic B6.129S7-Rag1tm1Mom/J mice and glycemia and weight were measured weekly. An oral glucose tolerance test was administered when mice reached normoglycemia. Co-transplantation of NPIs and MSCs resulted in earlier reversal of diabetes, improved glucose tolerance, higher insulin content and improved vascularization. One experiment conducted with MSCs from a donor with an autoimmune disease resulted in no improved transplant outcomes. Co-transplantation of human MSCs with NPIs is demonstrated to have a beneficial effect on transplant outcomes, likely due to improved early vascularization and islet insulin secretion. Furthermore, donor pathology can impact MSC properties.
Language
English
DOI
doi:10.7939/R36T0H926
Rights
This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for the purpose of private, scholarly or scientific research. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
Citation for previous publication
Hayward, JA, Ellis CE, Seeberger K, et al. Co-transplantation of mesenchymal stem cells with neonatal porcine islets improve graft function in diabetic mice. Diabetes Feb 28:doi:10.2337/db16-1068

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