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- Ström, Valter, et al.
(author)
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A novel and rapid method for quantification of magnetic nanoparticle-cell interactions using a desktop susceptometer
- 2004
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In: Nanotechnology. - : IOP Publishing. - 0957-4484 .- 1361-6528. ; 15:5, s. 457-466
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Journal article (peer-reviewed)abstract
- Activated endothelial cells (EC) are attractive prime targets for specific drug delivery using drug-carrying magnetic nanoparticles. In order to accomplish EC targeting, the interaction between magnetic particles and resting as well as activated endothelial cells must be characterized and quantified, because it will influence particle biodistribution, circulation half-time, and targeting efficacy. Here, we have quantified in vitro the interaction (adhesion/phagocytosis) between human endothelial cells and magnetite (Fe3O4) particles carrying different surface coatings with varying degrees of hydrophilicity and surface charge. Almost no adhesion was observed (about 1% or less) for three out of five particle types carrying plain dextran, carboxyl-substituted poly(ethylene glycol) and silica C18 coatings. In contrast, carboxyl-functionalized dextran and poly(ethylene glycol)-coated particles adhered or were phagocytosed to a considerable degree (58 and 26%, respectively). These clear and accurate results were obtained by measuring the magnetic response, i.e. magnetic susceptibility, from different fractions of the cell cultures as a means of determining the concentration of magnetic particles. Visible light and electron microscopy confirmed the magnetic quantification. To meet the need for a rapid yet sensitive instrument, we have developed a desktop magnetic susceptometer especially adapted for liquid samples or particles in a suspension. Despite its very high sensitivity, it is easy to operate and requires but a few seconds for a measurement. We also describe the construction and operation of this instrument.
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- Sumitran-Holgersson, S, et al.
(author)
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Activated porcine embryonic brain endothelial cells induce a proliferative human T-lymphocyte response
- 2003
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In: Cell Transplantation. - : SAGE Publications. - 1555-3892 .- 0963-6897. ; 12:6, s. 637-646
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Journal article (peer-reviewed)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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- Brevig, T, et al.
(author)
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Xenotransplantation for CNS repair : immunological barriers and strategies to overcome them
- 2000
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In: Trends in Neurosciences. - 0166-2236. ; 23:8, s. 44-337
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Journal article (peer-reviewed)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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