Normothermic machine perfusion (NMP) facilitates utilization of marginal liver allografts. It remains unknown whether clinical benefits offset additional costs in the real-world setting. We performed a comparison of outcomes and hospitalization costs for donor livers preserved by NMP versus static cold storage (SCS) at a high-volume center.
View Article and Find Full Text PDFSarcomas are a rare tumor of mesenchymal origin. The liposarcoma is the most common sarcoma of the retroperitoneum. Liposarcomas are typically low grade, and present at an advanced stage and a large size.
View Article and Find Full Text PDFUnlabelled: Successful intestinal transplantation is currently hindered by graft injury that occurs during procurement and storage, which contributes to postoperative sepsis and allograft rejection. Improved graft preservation may expand transplantable graft numbers and enhance posttransplant outcomes. Superior transplant outcomes have recently been demonstrated in clinical trials using machine perfusion to preserve the liver.
View Article and Find Full Text PDFBackground: Subnormothermic machine perfusion (SNMP) of liver grafts is currently less clinically developed than normothermic and hypothermic approaches, but may have logistical advantages. At intermediate temperatures, the oxygen demand of the graft is low enough to be satisfied with an acellular perfusate, obviating the need for oxygen carrying molecules. This intermediate metabolic rate, however, is sufficient to support the production of bile, which is emerging as an important indicator of graft injury and viability.
View Article and Find Full Text PDFPorcine islet xenotransplantation is a viable strategy to treat diabetes. Its translation has been limited by the pre-clinical development of a clinically available immunosuppressive regimen. We tested two clinically relevant induction agents in a non-human primate (NHP) islet xenotransplantation model to compare depletional versus nondepletional induction immunosuppression.
View Article and Find Full Text PDFBackground: Thrombosis is a known consequence of intraportal islet transplantation, particularly for xenogeneic islets. To define the origins of thrombosis after islet xenotransplantation and relate it to early inflammation, we examined porcine islets transplanted into non-human primates using a dual-transplant model to directly compare islet characteristics.
Methods: α1,3-Galactosyltransferase gene-knockout (GTKO) islets with and without expression of the human complement regulatory transgene CD46 (hCD46) were studied.
Xenotransplantation
November 2019
Background: Membrane cofactor protein CD46 attenuates the complement cascade by facilitating cleavage of C3b and C4b. In solid organ xenotransplantation, organs expressing CD46 have been shown to resist hyperacute rejection. However, the incremental value of human CD46 expression for islet xenotransplantation remains poorly defined.
View Article and Find Full Text PDFNaïve T cell activation requires antigen presentation combined with costimulation through CD28, both of which optimally occur in secondary lymphoid tissues such as lymph nodes and the spleen. Belatacept impairs CD28 costimulation by binding its ligands, CD80 and CD86, and in doing so, impairs de novo alloimmune responses. However, in most patients belatacept is ineffective in preventing allograft rejection when used as a monotherapy, and adjuvant therapy is required for control of costimulation-blockade resistant rejection (CoBRR).
View Article and Find Full Text PDFThe innate immune system is a critical regulator of the adaptive immune responses that lead to allograft rejection. It is increasingly recognized that endogenous molecules released from tissue injury and cell death are potent activators of innate immunity. Mitochondria, ancestrally related to bacteria, possess an array of endogenous innate immune-activating molecules.
View Article and Find Full Text PDFPig-to-human xenotransplantation offers a potential bridge to the growing disparity between patients with end-stage organ failure and graft availability. Early studies attempting to overcome cross-species barriers demonstrated robust humoral immune responses to discordant xenoantigens. Recent advances have led to highly efficient and targeted genomic editing, drastically altering the playing field towards rapid production of less immunogenic porcine tissues and even the discussion of human xenotransplantation trials.
View Article and Find Full Text PDFAntigen-experienced T cells, also known as memory T cells, are functionally and phenotypically distinct from naive T cells. Their enhanced expression of adhesion molecules and reduced requirement for co-stimulation enables them to mount potent and rapid recall responses to subsequent antigen encounters. Memory T cells generated in response to prior antigen exposures can cross-react with other nonidentical, but similar, antigens.
View Article and Find Full Text PDFType I diabetes remains a significant clinical problem in need of a reliable, generally applicable solution. Both whole organ pancreas and islet allotransplantation have been shown to grant patients insulin independence, but organ availability has restricted these procedures to an exceptionally small subset of the diabetic population. Porcine islet xenotransplantation has been pursued as a potential means of overcoming the limits of allotransplantation, and several preclinical studies have achieved near-physiologic function and year-long survival in clinically relevant pig-to-primate model systems.
View Article and Find Full Text PDFAim: The goal of this study was to assess the impact of recipient age on post-transplant outcome.
Methods: All pancreas transplants performed at Indiana University between 2003 and 2011 were reviewed. Demographic data were compared using standard chi-square and ANOVA testing.
Kidney paired donation (KPD) was first suggested in 1986, but it was not until 2000 when the first paired donation transplant was performed in the USA. In the past decade, KPD has become the fastest growing source of transplantable kidneys, overcoming the barrier faced by living donors deemed incompatible with their intended recipients. This review provides a basic overview of the concepts and challenges faced by KPD as we prepare for a national pilot program with the United Network for Organ Sharing.
View Article and Find Full Text PDFKidney paired donation is an evolving strategy for overcoming the incompatibility barrier inherent in living donor kidney transplantation. As evidence of the growing interest in this new approach, more than 800 paired donation transplants have been performed in the United States as of February 2010, greater than half of which were performed in 2008 and 2009. Recent advances in this field have incorporated non-directed or altruistic donors to initiate chains of transplants that are either performed simultaneously, or by utilizing "bridge donors" who continue a nonsimultaneous chain at a later date.
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