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Microencapsulation of Pancreatic Islets: A Non-Vascularised Transplantation Model
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Medical Cell Biology.
2008 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Transplantation of pancreatic islets is a potential treatment of type 1 diabetes that aims to restore normal blood glucose control. By encapsulating the islets in alginate, they can be protected from rejection. The aim of this thesis was to study the biology of encapsulated islets and to use the technique of microencapsulation to study the effect of transplantation in a system that is separated from direct contact with the vascular system and the host tissue at the transplantation site.

Encapsulated islets can effectively reverse hyperglycaemia after transplantation into the peritoneal cavity of diabetic mice. A period of culture before encapsulation and transplantation did not affect their insulin release or curative capability. Pre-culture with exendin-4 improved insulin secretion, but not to the extent that the long term outcome in our transplantation model was improved. Despite being able to reach and retain normoglycaemia, microencapsulated islets transplanted intraperitoneally decreased in size. More specifically the number of beta cells in each individual islet was decreased. However, in contrast to previous studies using non-encapsulated islets, the alpha cell number was maintained, and thus the capsule seems to protect these peripherally located and otherwise exposed cells. As the capsule also prevents revascularisation of the islets, the model was used to study the importance of vascular supply for islet amyloid formation. Islet amyloid is a possible reason for the long-term failure of transplanted islets. It is likely that their low vascular density causes a disturbed local clearance of IAPP and insulin that starts the aggregation of IAPP. Indeed, encapsulated islets had an accelerated amyloid formation compared to normal islets, and might serve as a model for further studies of this process.

In conclusion, although revascularisation is not a prerequisite for islet graft function, it plays an important role for islet transplantation outcome.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis , 2008. , p. 39
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 396
Keywords [en]
Microencapsulation, Islet transplantation, revascularisation, alpha-cell, exendin-4, islet amyloid
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-9369ISBN: 978-91-554-7338-9 (print)OAI: oai:DiVA.org:uu-9369DiVA, id: diva2:172835
Public defence
2008-12-05, B7:101a, BMC, Husargatan 3, Uppsala, 13:15
Opponent
Supervisors
Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2022-01-28Bibliographically approved
List of papers
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4. Extensive amyloid formation in transplanted microencapsulated mouse and human islets
Open this publication in new window or tab >>Extensive amyloid formation in transplanted microencapsulated mouse and human islets
2012 (English)In: Amyloid: Journal of Protein Folding Disorders, ISSN 1350-6129, E-ISSN 1744-2818, Vol. 19, no 2, p. 87-93Article in journal (Refereed) Published
Abstract [en]

Objective: Deposition of cell toxic islet amyloid is a frequent finding in type 2 diabetes and also in transplanted human islets, where it is a possible explanation for their long-term failure. One suggested reason for amyloid in transplanted islets is that their low vascular density results in a disturbed local clearance of islet amyloid polypeptide (IAPP). To test this hypothesis we analysed accumulation of amyloid in microencapsulated islets, which exemplify a non-vascularised islet graft.

Methods: Isolated islets from human or transgenic mice expressing human IAPP were microencapsulated in alginate and cultured in vitro or transplanted under the kidney capsule of normoglycemic nude mice. The degree of amyloid was determined after Congo red staining and subcellular alterations were analysed with electron microscopy.

Results: Insulin and IAPP secretion from transgenic mouse islets were markedly increased during stimulation with glucose after one week of culture, but encapsulated islets in general released less insulin. Amyloid was detected after both one and three weeks of culture in the transgenic mouse islets and the encapsulated islets were most affected. After transplantation, electron microscopy displayed both intra-and extracellular amyloid in microencapsulated as well as in non-encapsulated human and transgenic mouse islet grafts. However, amyloid was more frequent in the encapsulated grafts.

Conclusion: Micro-encapsulation of pancreatic islets might serve as an important tool for studies of amyloid formation under enhanced circumstances.

Keywords
Alginate, IAPP, islet amyloid, islet transplantation, islet amyloid polypeptide, microencapsulation
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:uu:diva-97772 (URN)10.3109/13506129.2012.679988 (DOI)000304521800005 ()
Available from: 2008-11-13 Created: 2008-11-13 Last updated: 2017-12-14Bibliographically approved

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