Genetic strategies to bring islet xenotransplantation to the clinic
CURRENT OPINION IN ORGAN TRANSPLANTATION
Authors: Hawthorne, Wayne J.; Lew, Andrew M.; Thomas, Helen E.
Abstract
Purpose of reviewDespite the benefits of islet and pancreas allotransplantation, their widespread use in type 1 diabetes is limited because of the paucity of suitable donors. Porcine xenotransplantation offers an alternative, and advances in genetic modification of pigs have opened up new potential for its clinical use. This review outlines the barriers to successful islet xenotransplantation, and genetic modifications that have been tested to overcome these.Recent findingsIslets from pigs lacking 1,3-galactosyltransferase, to prevent hyperacute rejection, are now used as a background strain for further genetic modifications. The instant blood-mediated inflammatory reaction is overcome by expressing complement regulators including CD46, CD55 and CD59. Prevention of immune-mediated rejection mediated by T cells, macrophages and natural killer cells remains a challenge. The use of immunosuppressive antibodies, such as anti-CD154 or anti-CD2, can be protective, and may be useful if they are produced by the islets themselves.SummaryThe field of xenotransplantation has benefited enormously from the development of new genetic modification strategies. With the possibility of multiple genetic modifications in the same animal, and a detailed knowledge of the mechanism of xenograft rejection, the challenge now is to develop islets that provide long-term graft survival without systemic immunosuppression.
Quantification of A. fumigatus-specific CD154(+) T-cells-preanalytic considerations
MEDICAL MYCOLOGY
Authors: Wurster, S.; Weis, P.; Page, L.; Lazariotou, M.; Einsele, H.; Ullmann, A. J.
Abstract
Fungal specific CD154(+) T-cells have been described as a biomarker in invasive aspergillosis. The influence of sample storage on the detection of these cells was assessed. Six-hour delay prior to PBMC isolation is associated with an 18% decrease of cell viability and alterations of the cellular composition of the sample. This results in 87% reduction of CD154(+) A. fumigatus specific cells due to reduced assay sensitivity and increased background values in unstimulated samples. If prompt cell measurement is not feasible, isolated PBMCs can be frozen (at -20 degrees C and -80 degrees C) and processed later with comparable assay reliability (mean value fresh vs. thawing: 0.126, 0.133; Pearson-Coefficient: 0.962).
COA
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