American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons
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The success of clinical transplantation as a therapy for end-stage organ failure is limited by the availability of suitable organs for transplant. This article discusses continued efforts by the transplant community to collaboratively improve the organ supply. There were 7593 deceased organ donors in 2005. ⋯ The percentage of deceased donations that occurred following cardiac death has also reached a new high at 7%. The number of living donors decreased by 2%, from 7003 in 2004 to 6895 in 2005. This article discusses the continued efforts of the Organ Donation Breakthrough Collaborative and the Organ Transplantation Breakthrough Collaborative to support organ recovery and use and to encourage the expectation that for every deceased donor, all organs will be placed and transplanted.
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Renal tubular epithelial cells (TEC) die by apoptosis or necrosis in renal ischemia-reperfusion injury (IRI). Fas/Fas ligand-dependent fratricide is critical in TEC apoptosis, and Fas promotes renal IRI. Therefore, targeting Fas or caspase-8 may have therapeutic potential for renal injury in kidney transplant or failure. ⋯ Inferior vena cava delivery of pHEX-small interfering RNA targeting Fas or pro-caspase-8 resulted in protection of kidney from IRI, indicated by reduction of renal tubular injury (necrosis and apoptosis) and serum creatinine or blood urea nitrogen. Our data suggest that shRNA-based therapy targeting Fas and caspase-8 in renal cells can lead to protection of kidney from IRI. Attenuation of pro-apoptotic proteins using genetic manipulation strategies such as shRNA might represent a novel strategy to promote kidney allograft survival from rejection or failure.
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Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. ⋯ Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.
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Reduced intensity conditioning (RIC) prior to allogeneic hematopoietic cell transplantation (HCT) has shown promise in lowering the incidence of post-transplant complications including infection and graft-versus-host disease. T-cell-mediated graft rejection, however, remains a crucial factor in determining how 'mild' a level of immunosuppression can be administered. Understanding the kinetics of resistance responses as well as the role of CD4+ and CD8+ T cells underlies the development of protocols to circumvent resistance and support hematopoietic engraftment. ⋯ Host CD4+ T cells were required for optimal expansion of specific (H60) T-cell receptor (TCR) expressing host anti-donor MiHA reactive CD8+ T cells following HCT. These observations demonstrate a critical role for host CD4+ T cells in resistance against MiHA disparate HCT. This RIC HCT resistance model will be useful for the analysis of the barrier to engraftment mediated by host T cells and the development of strategies to support engraftment.
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The liver organ allocation policy of the United Network for Organ Sharing (UNOS) is based on the model for end-stage liver disease (MELD). The policy provides additional priority for candidates with hepatocellular carcinoma (HCC) who are awaiting deceased donor liver transplantation (DDLT). However, this priority was reduced on February 27, 2003 to a MELD of 20 for stage T1 and of 24 for stage T2 HCC. ⋯ Regional differences in rates of DDLT for HCC were observed during both MELD periods. Consequently, the reduced MELD score for stage T1 and T2 HCC candidates awaiting DDLT has not had an impact nationally either on their survival on the waiting list or on their ability to obtain a liver transplant within a reasonable time frame. However, regional variations point to the need for reform in how organs are allocated for HCC at the regional level.