Response of encapsulated rat pancreatic islets to hypoxia

Hypoxia contributes to encapsulated pancreatic islet graft failure. To gain insight into the mechanisms that lead to hypoxia-induced graft failure, encapsulated islet function, vitality, and cell replication were assessed after 2 and 5 days of hypoxic (1% O-2) and normoxic (20% O-2) culture. The mRNA expression levels of Bcl-2, Bax, inducible nitric oxide synthase (iNOS), and monocyte chemoattractant protein I (MCP-1) were assessed, as well as the amount of nitrite and MCP-1 in the culture medium. Hypoxia was associated with loss of encapsulated islet function and vitality, but not with an increase in islet cell replication. Loss of vitality was due to necrosis', and only modestly due to apoptosis. Hypoxia was not associated with changes in the Bcl-2/Bax mRNA ratio, but it did increase the expression of iNOS and MCP-1 mRNA. The increased mRNA levels were, however, not associated with elevated concentrations of nitrite nor with elevated levels of MCPI protein. The increased iNOS mRNA levels imply a role for NO in the completion of cell death by hypoxia. The increased MCP-1 mRNA levels suggest that encapsulated islets in vivo contribute to their own graft failure by attracting cytokine-producing macrophages. The discrepancy between iNOS mRNA and nitrite is explained by the longer half-life of NO during hypoxia. MCP-1 protein levels are underestimated as a consequence of the lower number of vital cells in combination with a higher proteolytic activity due to necrosis. Thus, strategies to eliminate hypoxia may not only improve islet function and vitality, but may also reduce the attraction of macrophages by encapsulated islets

Mesenchymal stromal cell treatment of donor kidneys during ex-vivo normothermic machine perfusion:A porcine renal autotransplantation study

Normothermic machine perfusion (NMP) of injured kidneys offers the opportunity for interventions to metabolically active organs prior to transplantation. Mesenchymal stromal cells (MSCs) can exert regenerative and anti-inflammatory effects in ischaemia-reperfusion injury. The aims of this study were to evaluate the safety and feasibility of MSC treatment of kidneys during NMP using a porcine auto-transplantation model, and examine potential MSC treatment-associated kidney improvements up to 14 days post transplantation. After 75 minutes of kidney warm ischaemia, four experimental groups of n=7 underwent 14 hours of oxygenated hypothermic machine perfusion. In three groups this was followed by 240 minutes of NMP with infusion of vehicle, ten million porcine or ten million human adipose derived MSCs. All kidneys were auto-transplanted after contralateral nephrectomy. MSC treatment did not affect perfusion haemodynamics during NMP or cause adverse effects at reperfusion, with 100% animal survival. MSCs did not affect plasma creatinine, glomerular filtration rate, neutrophil gelatinase-associated lipocalin concentrations or kidney damage assessed by histology during the 14 days, and MSCs retention was demonstrated in renal cortex. Infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. Within the short post- transplant

Organ preservation solutions: clinical and pharmaceutical aspects

Systematic research has led to continuing improvements in the solutions and techniques of preserving donated hearts. The persistent shortage of donors means that organs of lower quality are increasingly being accepted and we are turning more and more to machine perfusion of donated hearts

New solutions in organ preservation

Over the last 20 years, a number of methods and solutions have been developed to preserve donor organs for transplantation. Collins et al first introduced the simple cold-storage technique to store and transport kidneys up to 30 hours. The development of the University of Wisconsin cold-storage solution (UW-CSS) in 1986 improved organ preservation and resulted in a better understanding in preservation related injury. Since its introduction, several UW-CSS-derived solutions have been tested, and important components for hypothermic preservation were identified. Pathophysiologic mechanisms in static hypothermic preserved organs are discussed, including hypothermia-induced cell swelling, compromised membrane function, adenosine triphosphate usage, cellular acidosis, and prevention of precursor formation of reactive oxygen species. Counteracting these pathophysiologic mechanisms can be divided into components acting by two protective principles. The first is to create a physical environment, minimizing cellular and interstitial edema formation. The second mechanism involves biochemically active components that ideally enter the cell and remain effective during reperfusion. Some preservation solutions currently in use are discussed on the basis of these two protective mechanisms. In respect of these principles in preservation, new solutions in preservation are discussed. Although cold-storage solutions improved organ viability, maintaining or even improving organ quality during preservation remains an important goal. Future advances in preservation might be found in donor pretreatment, cytoprotection, or the use of dynamic preservation systems. © 2002 Elsevier Science (USA). All rights reserved

Propionate induced effects on feed intake and blood parameters in sheep

International audienc

Systematic review on the treatment of deceased organ donors

Background Currently, there is no consensus on which treatments should be a part of standard deceased-donor management to improve graft quality and transplantation outcomes. The objective of this systematic review was to evaluate the effects of treatments of the deceased, solid-organ donor on graft function and survival after transplantation. Methods Pubmed, Embase, Cochrane, and Clinicaltrials.gov were systematically searched for randomized controlled trials that compared deceased-donor treatment versus placebo or no treatment. Results A total of 33 studies were selected for this systematic review. Eleven studies were included for meta-analyses on three different treatment strategies. The meta-analysis on methylprednisolone treatment in liver donors (two studies, 183 participants) showed no effect of the treatment on rates of acute rejection. The meta-analysis on antidiuretic hormone treatment in kidney donors (two studies, 222 participants) indicates no benefit in the prevention of delayed graft function. The remaining meta-analyses (seven studies, 334 participants) compared the effects of 10 min of ischaemic preconditioning on outcomes after liver transplantation and showed that ischaemic preconditioning improved short-term liver function, but not long-term transplant outcomes. Conclusions There is currently insufficient evidence to conclude that any particular drug treatment or any intervention in the deceased donor improves long-term graft or patient survival after transplantation