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Restoration of Islet Vascularity and Oxygenation in Mouse and Human Islets Experimentally Transplanted to the Omentum: A Basis for Superior Function when Compared to Intraportally Transplanted Islets
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi. Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinska vetenskaper, Transplantation och regenerativ medicin. (Per-Ola Carlsson)
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
Uppsala universitet, Medicinska och farmaceutiska vetenskapsområdet, Medicinska fakulteten, Institutionen för medicinsk cellbiologi.
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2016 (Engelska)Ingår i: American Journal of Transplantation, ISSN 1600-6135, E-ISSN 1600-6143Artikel i tidskrift (Refereegranskat) Submitted
Ort, förlag, år, upplaga, sidor
2016.
Nyckelord [en]
Islet transplantation, omentum, engraftment
Nationell ämneskategori
Cell- och molekylärbiologi
Forskningsämne
Medicinsk cellbiologi
Identifikatorer
URN: urn:nbn:se:uu:diva-282948OAI: oai:DiVA.org:uu-282948DiVA, id: diva2:917909
Forskningsfinansiär
Vetenskapsrådet, 55X-15043Tillgänglig från: 2016-04-08 Skapad: 2016-04-08 Senast uppdaterad: 2018-01-10Bibliografiskt granskad
Ingår i avhandling
1. Engraftment of Pancreatic Islets in Alternative Transplantation Sites and the Feasibility of in vivo Monitoring of Native and Transplanted Beta-Cell Mass
Öppna denna publikation i ny flik eller fönster >>Engraftment of Pancreatic Islets in Alternative Transplantation Sites and the Feasibility of in vivo Monitoring of Native and Transplanted Beta-Cell Mass
2016 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Islet transplantation is a possible curative treatment for type 1 diabetes (T1D). Currently the liver dominates as implantation site, despite the many challenges encountered at this site.

Acute hypoxia in islets transplanted to muscle and omentum, two possible alternative sites, was prevailing. However, it was rapidly reversed at both implantation sites, in contrast to when islets were transplanted intraportally. At the intramuscular site hypoxia was further relieved by co-transplantation of an oxygen carrier, polymerized hemoglobin, which also improved the functional outcome. The complement system was activated after islet transplantation to muscle, but did not hamper graft function.

Both mouse and human islets transplanted to omentum become well re-vascularized and have a functional blood flow and oxygenation comparable with that of endogenous islets. Animals transplanted with islets to the omentum had a superior graft function compared with animals receiving intraportal islet grafts.

Alloxan-diabetic animals were cured with a low number of islets both when the islets were implanted in the omentum and muscle. The islet grafts responded adequately to both glucose and insulin and displayed a favorable mRNA gene expression profile.

A challenge in diabetes research and in islet transplantation is that there are no established techniques for quantifying beta-cell mass in vivo. By using radiolabeled Exendin-4, a GLP-1 receptor agonist, beta-cell mass after transplantation to muscle of mice was quantified. The results may well be translated to the clinical setting.

By comparing the pancreatic accumulation of [11C]5-hydroxy tryptophan ([11C]5-HTP) as detected by positron emission tomography (PET) in T1D patients with that of healthy controls, a 66% decrease was observed. This may in fact represent the loss of beta-cells, taking into account that other cells within the islets of Langerhans are largely unaffected in T1D. 

In conclusion, the data presented support the use of alternative implantation sites for islet transplantation. In addition to improving the functional outcome this may enable more transplantations since the number of transplanted islets may be reduced. The techniques investigated for quantifying transplanted and endogenous beta-cell mass may greatly improve our knowledge of the pathophysiology of T1D and become a valuable tool for evaluation of beta-cell mass.

Ort, förlag, år, upplaga, sidor
Uppsala: Acta Universitatis Upsaliensis, 2016. s. 88
Serie
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1211
Nyckelord
Type 1 diabetes, Islet transplantation, Alternative implantation sites, Exendin-4, Positron Emission Tomography, 5-hydroxy tryptophan, Beta-cell mass
Nationell ämneskategori
Cell- och molekylärbiologi
Forskningsämne
Medicinsk cellbiologi
Identifikatorer
urn:nbn:se:uu:diva-282953 (URN)978-91-554-9551-0 (ISBN)
Disputation
2016-06-01, Sal B22, BMC, Husargatan 3, Uppsala, 09:15 (Engelska)
Opponent
Handledare
Tillgänglig från: 2016-05-11 Skapad: 2016-04-08 Senast uppdaterad: 2018-01-10

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Espes, DanielQuach, MyChristoffersson, GustafCarlsson, Per-Ola

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Institutionen för medicinsk cellbiologiTransplantation och regenerativ medicin
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