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Isolation of mouse-to-rat cardiac xenograft-infiltrating cells by ex vivo propagation
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Transplantation Surgery.
2002 (English)In: Xenotransplantation, Vol. 9, no 3, 209-219 p.Article in journal (Refereed) Published
Place, publisher, year, edition, pages
2002. Vol. 9, no 3, 209-219 p.
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-90061OAI: oai:DiVA.org:uu-90061DiVA: diva2:162146
Available from: 2002-11-21 Created: 2002-11-21 Last updated: 2015-06-15Bibliographically approved
In thesis
1. Studies of Rejection in Experimental Xenotransplantation
Open this publication in new window or tab >>Studies of Rejection in Experimental Xenotransplantation
2002 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

One main hurdle to xenotransplantation, i.e. transplantation between different species, is the immunological barrier that the organ meets in the recipient. The aim of this thesis was to characterise xenogeneic rejection mechanisms by using the concordant mouse-to-rat heart transplantation model.

Graft-infiltrating immune cells could be isolated from both rejecting and non-rejecting grafts using ex vivo propagation, a technique based on incubation of graft biopsies in culture medium for 48 hours. The numbers of recovered T lymphocytes were considerably higher in grafts undergoing cell-mediated rejection than in grafts undergoing acute vascular rejection (AVR) or in non-rejecting transplants. Thus, ex vivo propagation should be a valuable tool for further studies of cell-mediated rejection.

Cytokine patterns in the grafts, as measured by a quantitative real-time RT-PCR method, showed that AVR and cell-mediated rejection are associated with an increase of both pro-inflammatory cytokines (IL-1β and TNF-α) and more specific cytokines (IL-2, IL-10, IL-12p40 and IFN-γ). These data differed considerably from the patterns seen in the spleens of the recipients. Cell-mediated xenograft rejection was also found to be associated with a local accumulation of hyaluronan.

Oral administration of xenogeneic cells stimulated a production of antibodies that could induce hyperacute rejection of cardiac xenografts when passively transferred to graft recipients. This is in contrast to several models for autoimmune diseases and allogeneic transplantation where oral administration of antigens is an effective way to induce unresponsiveness. Hence, future attempts to induce oral tolerance in xenotransplantation should be done with caution.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2002. 60 p.
Series
Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 0282-7476 ; 1211
Keyword
Surgery, Antibodies, cell culturing, cytokines, hyaluronan, immunosuppression, mouse, rat, rejection, T lymphocytes, xenotransplantation., Kirurgi
National Category
Surgery
Research subject
Surgery
Identifiers
urn:nbn:se:uu:diva-2891 (URN)91-554-5476-3 (ISBN)
Public defence
2002-12-13, Rosénsalen, Akademiska sjukhuset, ingång 95/96, Uppsala, 09:15
Opponent
Available from: 2002-11-21 Created: 2002-11-21 Last updated: 2013-06-19Bibliographically approved

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Lorant, TomasTufveson, Gunnar

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