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Composite islet-endothelial cell grafts: a novel approach to counteract innate immunity in islet transplantation.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
Uppsala University, Medicinska vetenskapsområdet, Faculty of Medicine, Department of Oncology, Radiology and Clinical Immunology. KITM.
2005 (English)In: Am J Transplant, ISSN 1600-6135, Vol. 5, no 11, 2632-9 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2005. Vol. 5, no 11, 2632-9 p.
Keyword [en]
Animals, Cell Culture Techniques/methods, Endothelial Cells/*transplantation, Graft Survival/immunology, Humans, Islets of Langerhans/*cytology, Islets of Langerhans Transplantation/*immunology, Mice, Mice; Nude, Subrenal Capsule Assay, Transplantation; Heterologous/*physiology
Identifiers
URN: urn:nbn:se:uu:diva-25563PubMedID: 16212622OAI: oai:DiVA.org:uu-25563DiVA: diva2:53337
Available from: 2007-02-13 Created: 2007-02-13 Last updated: 2011-01-12
In thesis
1. Formation of Composite Islet Grafts: A novel strategy to promote islet survival and revascularization
Open this publication in new window or tab >>Formation of Composite Islet Grafts: A novel strategy to promote islet survival and revascularization
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The islets of Langerhans are small and delicate spheroid organs scattered in the pancreas responsible for insulin production. Transplantation of isolated islets is a beneficial therapy for patients with a severe form of type 1 diabetes. The islets, which normally are richly vascularized in the pancreas, are completely disconnected from the vascular support by the enzymatic digestion during the isolation procedure. Islet viability is affected throughout all steps in this process, from donor death and isolation of islets to culturing and the transplantation process itself.

In this thesis a novel strategy to promote islet survival and to re-establish islet vasculature is presented. We show endogenous expression of 51 different genes related to inflammation in cultured islets. Among these genes high expression of MCP-1, MIF, VEGF, thymosin b-10 and IL-8, IL-1β, IL-5R-a, IFN-γ antagonist were found in all donors during the 5- and the 2-day cultures, respectively. Protein expression of these genes can stimulate inflammatory immune responses but also promote tissue repair by attracting curative cells such as endothelial cells (EC) leading to re-establishment of the vasculature.

We have established a novel technique by formation of composite islets using EC and mesenchymal stem cells (MSC). EC adhered on the surface of the islets and created a potential blood tolerant surface. The EC-islets showed a degree of protection from the detrimental effects of instant blood-mediated inflammatory reaction (IBMIR) with the major components of IBMIR being decreased in in vitro assays. We combined MSC to the EC-islets with success. The MSC were found to have proliferative effect on EC and the combination of these two cell types on the islets further increased the EC covered surface compared to EC-islets. The EC-MSC-islets in co-culture formed vessel-like structures both into the islets and out to the surrounding matrix. The MSC enhanced the exogenous EC to form vessel-like network in the EC-MSC-islets indicating vascular support by the MSC.

The novel strategy and conditions presented herein could alleviate problems related to survival of the islets by promoting revascularization. This would open up a new era in islet transplantation and allow more patients to benefit from this therapy.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2009. 67 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 463
Series
Keyword
Islet of Langerhans, cytokines and cytokinereceptors expression, endothelial cells, mesenchymal stromal cells, transplantation, revascularization
National Category
Immunology in the medical area
Research subject
cellforskning
Identifiers
urn:nbn:se:uu:diva-102788 (URN)978-91-554-7551-2 (ISBN)
Public defence
2009-06-12, Rudbecksalen, Daghammarskjöldsv. 20, UPPSALA, 09:15 (English)
Opponent
Supervisors
Projects
Clinical immunology, islet group
Available from: 2009-05-20 Created: 2009-05-11 Last updated: 2009-05-20Bibliographically approved

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Johansson, UlrikaElgue, GracielaKorsgren, Olle

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