Allogeneic islet transplantation has proven difficult because organ shortages are recurrent, several pancreas donors are often needed to treat one diabetic recipient, and the intrahepatic site of islet implantation may not be the most appropriate site. Thus, another source of insulin-producing cells would be beneficial; and pigs represent a possible and viable source for obtaining such cells. Although the use of pig islet grafts appears to be difficult because of the species barrier, recent reports demonstrated that pig islet xenotransplantation can overcome the immunological barrier following strong immunosuppression and function successfully in primates for at least 6 months. Before becoming clinically applicable, however, pig islet xenotransplantation must still overcome the structural and physiological incompatibility between pig donor and human recipient. Researchers agree that it is necessary to produce more preclinical data in the pig-to-primate model before any pig-to-human transplantation of islets can be considered. Therefore, in this review, we provide a summary of the present state of knowledge about pig and human islet compatibility.
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http://dx.doi.org/10.1016/j.trre.2011.07.004 | DOI Listing |
Transpl Int
January 2025
Pôle de Chirurgie Expérimentale et Transplantation, Université Catholique de Louvain, Brussels, Belgium.
Clinical pancreatic islet xenotransplantation will most probably rely on genetically modified pigs as donors. Several lines of transgenic pigs carrying one and more often, multiple modifications already exist. The vast majority of these modifications aim to mitigate the host immune response by suppressing major xeno-antigens, or expressing immunomodulatory molecules that act locally at the graft site.
View Article and Find Full Text PDFTranspl Int
December 2024
Molecular Animal Breeding and Biotechnology, Gene Center and Department of Veterinary Sciences, LMU Munich, Munich, Germany.
Xenotransplantation of porcine organs has made remarkable progress towards clinical application. A key factor has been the generation of genetically multi-modified source pigs for xenotransplants, protected against immune rejection and coagulation dysregulation. While efficient gene editing tools and multi-cistronic expression cassettes facilitate sophisticated and complex genetic modifications with multiple gene knockouts and protective transgenes, an increasing number of independently segregating genetic units complicates the breeding of the source pigs.
View Article and Find Full Text PDFEJNMMI Res
December 2024
Department of Medical Cell Biology, Department of Medical Sciences, Science for Life Laboratory, Uppsala University, Box 571, 75123, Uppsala, Sweden.
Background: Type 1 diabetes (T1D) is an autoimmune disease characterized by a progressive β-cell destruction. There are no clinically established methods for quantifying endocrine cells of the pancreas and current knowledge is almost exclusively based on autopsy material and functional measurements. Based on the expression of the γ-aminobutyric acid A receptors (GABARs) in pancreatic islets and the fact that GABAR agonists are being explored as treatment for T1D, we hypothesized that the positron emission tomography (PET) tracer [C]flumazenil ([C]FMZ) could serve as a marker of the endocrine mass of the pancreas.
View Article and Find Full Text PDFAm J Transplant
November 2024
Isla Technologies, Inc, San Carlos, California, USA. Electronic address:
In this study using a discordant, xenogeneic, transplant model we demonstrate the functionality and safety of the first stent-based bioartificial pancreas (BAP) device implanted endovascularly into an artery, harnessing the high oxygen content in blood to support islet viability. The device is a self-expanding nitinol stent that is coated with a bilayer of polytetrafluoroethylene that forms channels to hold islets embedded in a hydrogel. We completed a 1-month study in the nondiabetic swine model (N = 3) to test the safety of the device and to assess islet functionality after device recovery.
View Article and Find Full Text PDFTranspl Int
November 2024
Clinic Unit of Regenerative Medicine and Organ Transplants and Diabetes Research Institute, Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS) Ospedale San Raffaele, Milan, Italy.
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