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- Brevig, T, et al.
(författare)
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Xenotransplantation for CNS repair : immunological barriers and strategies to overcome them
- 2000
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Ingår i: Trends in Neurosciences. - 0166-2236. ; 23:8, s. 44-337
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Tidskriftsartikel (refereegranskat)abstract
- Neural transplantation holds promise for focal CNS repair. Owing to the shortage of human donor material, which is derived from aborted embryos, and ethical concerns over its use, animal donor tissue is now considered an appropriate alternative. In the USA, individuals suffering from Parkinson's disease, Huntington's disease, focal epilepsy or stroke have already received neural grafts from pig embryos. However, in animal models, neural tissue transplanted between species is usually promptly rejected, even when implanted in the brain. Some of the immunological mechanisms that underlie neural xenograft rejection have recently been elucidated, but others remain to be determined and controlled before individuals with neurological disorders can benefit from xenotransplantation.
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- Sumitran-Holgersson, S, et al.
(författare)
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Activated porcine embryonic brain endothelial cells induce a proliferative human T-lymphocyte response
- 2003
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Ingår i: Cell Transplantation. - : SAGE Publications. - 1555-3892 .- 0963-6897. ; 12:6, s. 637-646
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Tidskriftsartikel (refereegranskat)abstract
- Transplantation of allogeneic embryonic neural tissue is a potential treatment for patients with Parkinson's and Huntington's diseases. The supply of human donor tissue is limited, and alternatives such as the use of animal (e.g., porcine) donor tissue are currently being evaluated. Before porcine grafts can be used clinically, strategies to prevent neural xenograft rejection must be developed. Knowledge on how human T lymphocytes recognize porcine embryonic neural tissue would facilitate the development of such strategies. To investigate the ability of porcine embryonic brain microvascular endothelial cells (PBMEC) to stimulate human T-cell proliferation, PBMEC were immuno-magnetically isolated and cocultured with purified human CD4 or CD8 single-positive T cells. PBMEC had a cobblestone-like growth pattern and expressed the endothelial cell markers CD31 and CD106. PBMEC stimulated with the supernatant of phytohemagglutinin-activated porcine peripheral blood mononuclear cells or porcine IFN-gamma, but not nonstimulated PBMEC, induced proliferation of both CD8 and CD4 T cells as assessed by [H-3]thymidine incorporation. Flow cytometric analyses showed that the degree of CD8 and CD4 T cell proliferation correlated with the expression levels of class I and 11 major histocompatibility complex (MHC) antigens, respectively. PBMEC expressed a CTLA-4/Fc-reactive molecule, most likely CD86, suggesting that these cells are able to deliver a costimulatory signal to the T cells. Human TNF-alpha, but not human IFN-gamma, induced class I, but not class II, MHC expression on PBMEC. Within a neural graft or the regional lymph nodes, PBMEC might stimulate human T cells via the direct pathway, and should therefore be removed from the donor tissue prior to transplantation.
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