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ex vivo renal perfusion

Xiangyu Zou, Kai Jiang, Amrutesh S Puranik, Kyra L Jordan, Hui Tang, Xiangyang Zhu, Lilach O Lerman
Mesenchymal stem cells (MSC) have been experimentally used for kidney repair, but modest retention limits their efficacy. Cell-surface coating allows modulating MSC homing and interaction with target cells. We coated mouse adipose tissue-derived MSC with antibodies directed against kidney injury molecule-1 (ab-KIM1), which is upregulated in injured kidneys, and tested the hypothesis that this would enhance their therapeutic effects in ischemic kidney injury. Untreated MSC, ab-KIM1-coated MSC (KIM-MSC), or vehicle, were injected systemically into the carotid artery of 2-kidneys, 1-clip mice 2 weeks after surgery...
February 15, 2018: Stem Cells Translational Medicine
Xiangyu Zou, Soon Hyo Kwon, Kai Jiang, Christopher M Ferguson, Amrutesh S Puranik, Xiangyang Zhu, Lilach O Lerman
To test the hypothesis that intrinsic renal scattered tubular cells (STC-like cells) contribute to repairing injured tubular epithelial cells (TEC) by releasing extracellular vesicle (EV). EV released from primary cultured pig STC-like cells were confirmed by electron microscopy. Antimycin-A (AMA)-induced injured proximal TEC (PK1 cells) were co-cultured with STC-like cells, STC-like cells-derived EV, or EV-free conditioned-medium for 3 days. Cellular injury, oxidative stress and mitochondrial function were assessed...
January 19, 2018: Scientific Reports
Charlotte von Horn, Thomas Minor
Within the scope of transplantation research, ex vivo kidney perfusion has been proven an attractive model to study ischemia-reperfusion and preservation injury. Renal perfusion techniques also occupy scientists with the aim to optimize organ reconditioning and preparation prior to transplantation. This study investigated the influence of a pulsatile perfusion pattern that brings flow conditions closer to physiological situations, on renal perfusion characteristic and kidney function in the isolated perfused kidney...
January 4, 2018: Scandinavian Journal of Clinical and Laboratory Investigation
S A Hosgood, E Thompson, T Moore, C H Wilson, M L Nicholson
BACKGROUND: A significant proportion of donation after circulatory death (DCD) kidneys are declined for transplantation because of concerns over their quality. Ex vivo normothermic machine perfusion (NMP) provides a unique opportunity to assess the quality of a kidney and determine its suitability for transplantation. METHODS: In phase 1 of this study, declined human DCD kidneys underwent NMP assessment for 60 min. Kidneys were graded 1-5 using a quality assessment score (QAS) based on macroscopic perfusion, renal blood flow and urine output during NMP...
March 2018: British Journal of Surgery
Gregory T Tietjen, Sarah A Hosgood, Jenna DiRito, Jiajia Cui, Deeksha Deep, Eric Song, Jan R Kraehling, Alexandra S Piotrowski-Daspit, Nancy C Kirkiles-Smith, Rafia Al-Lamki, Sathia Thiru, J Andrew Bradley, Kourosh Saeb-Parsy, John R Bradley, Michael L Nicholson, W Mark Saltzman, Jordan S Pober
Ex vivo normothermic machine perfusion (NMP) is a new clinical strategy to assess and resuscitate organs likely to be declined for transplantation, thereby increasing the number of viable organs available. Short periods of NMP provide a window of opportunity to deliver therapeutics directly to the organ and, in particular, to the vascular endothelial cells (ECs) that constitute the first point of contact with the recipient's immune system. ECs are the primary targets of both ischemia-reperfusion injury and damage from preformed antidonor antibodies, and reduction of perioperative EC injury could have long-term benefits by reducing the intensity of the host's alloimmune response...
November 29, 2017: Science Translational Medicine
Sarah A Hosgood, Tom Moore, Theresa Kleverlaan, Tom Adams, Michael L Nicholson
BACKGROUND: Ex-vivo normothermic perfusion strategies are a promising new instrument in organ transplantation. The perfusion conditions are designed to be protective however the artificial environment can induce a local inflammatory response. The aim of this study was to determine the effect of incorporating a Cytosorb adsorber into an isolated kidney perfusion system. METHODS: Porcine kidneys were subjected to 22 h of cold ischaemia then reperfused for 6 h on an ex vivo reperfusion circuit...
October 25, 2017: Journal of Translational Medicine
Stephanie F Smith, Thomas Adams, Sarah A Hosgood, Michael L Nicholson
BACKGROUND: Argon has shown potential as an organoprotective agent in numerous models of ischemia-reperfusion injury (IRI). The aim of this study was to evaluate the effects of argon gas during ex vivo normothermic perfusion (EVNP) in an experimental porcine model of kidney IRI. MATERIALS AND METHODS: After a warm ischemia time of 15 min and 17 h of static cold storage, porcine kidneys underwent 1 h of EVNP using leukocyte-depleted blood. During EVNP, kidneys were perfused with a gas composition either of 70% argon (n = 6), 70% nitrogen control (n = 6), or standard 95% oxygen (n = 6) balanced with 5% carbon dioxide...
October 2017: Journal of Surgical Research
Annemarie Weissenbacher, James Hunter
PURPOSE OF REVIEW: Normothermic machine perfusion (NMP) is a preservation method that is generating increasing interest. The aim of this review is to summarise the current status of NMP in regards of kidney viability assessment, reducing organ damage and improving transplant logistics. RECENT FINDINGS: The results of recent large animal experiments and clinical trials show that continuous prolonged normothermic ex-vivo kidney perfusion appears better than a brief period of NMP after static cold storage in terms of renal injury and function...
December 2017: Current Opinion in Organ Transplantation
J Moritz Kaths, Mátyás Hamar, Juan Echeverri, Ivan Linares, Peter Urbanellis, Jun Yu Cen, Sujani Ganesh, Luke S Dingwell, Paul Yip, Rohan John, Darius Bagli, Istvan Mucsi, Anand Ghanekar, David Grant, Lisa A Robinson, Markus Selzner
Normothermic ex vivo kidney perfusion (NEVKP) represents a novel approach for graft preservation and functional improvement in kidney transplantation. We investigated whether NEVKP also allows graft quality assessment before transplantation. Kidneys from 30-kg pigs were recovered in a model of heart-beating donation (group A) after 30 minutes (group B) or 60 minutes (group C) (n = 5/group) of warm ischemia. After 8 hours of NEVKP, contralateral kidneys were resected, grafts were autotransplanted, and the pigs were followed for 3 days...
September 10, 2017: American Journal of Transplantation
Stephan Rodrigo Marticorena Garcia, Markus Grossmann, Sophia Theresa Lang, Heiko Tzschätzsch, Florian Dittmann, Bernd Hamm, Jürgen Braun, Jing Guo, Ingolf Sack
PURPOSE: To measure normal renal stiffness in adults, taking into account regional variation, hydration, and urinary status. METHODS: Thirty-six healthy volunteers were examined by tomoelastography based on MR elastography at four frequencies, from 40 to 70 Hz and multifrequency shear wave speed recovery. Regional wave speeds were derived for the medulla, cortex (inner cortex and outer cortex), and renal pelvis, and examined for age-related effects. Subgroups were repeatedly examined for reproducibility, amount of prior water drinking, and urinary status...
August 30, 2017: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
Xiaona Liu, Na Li, Tao Xu, Fang Sun, Rui Li, Qimin Gao, Lianxiang Chen, Chaoyang Wen
BACKGROUND: To evaluate the effect of perfusion status on elasticity measurements of different compartments in the kidney using shear wave elastography (SWE) both in vivo and ex vivo. METHODS: Thirty-two rabbit kidneys were used to observe the elasticity variation caused by renal artery stenosis and vein ligation in vivo, and six beagle kidneys were studied ex vivo to explore the effect of renal perfusion on elasticity. Supersonic SWE was applied to quantify the elasticity values of different renal compartments (cortex, medulla and sinus)...
August 8, 2017: BMC Nephrology
Theodoros Kassimatis, Anass Qasem, Abdel Douiri, Elizabeth G Ryan, Irene Rebollo-Mesa, Laura L Nichols, Roseanna Greenlaw, Jonathon Olsburgh, Richard A Smith, Steven H Sacks, Martin Drage
BACKGROUND: Delayed graft function (DGF) is traditionally defined as the requirement for dialysis during the first week after transplantation. DGF is a common complication of renal transplantation, and it negatively affects short- and long-term graft outcomes. Ischaemia reperfusion injury (IRI) is a prime contributor to the development of DGF. It is well established that complement system activation plays a pivotal role in the pathogenesis of IRI. Mirococept is a highly effective complement inhibitor that can be administered ex vivo to the donor kidney just before transplantation...
June 6, 2017: Trials
Daniel Urcuyo, Matthew F Blum, Qiang Liu, Ahmed Nassar, Laura D Buccini, Teresa Diago Uso, Emilio D Poggio, William M Baldwin Iii, David A Goldfarb, Cristiano Quintini
PURPOSE: Ex vivo perfusion of marginal kidney grafts offers the chance to expand the donor pool, but there is no current clinical standard for the prolonged warm perfusion of renal grafts. This exploratory pilot study seeks to identify a stable ex vivo kidney perfusion model that can support low intravascular resistance and preserve histologic architecture in a porcine donation after cardiac death (DCD) model. METHODS: 15 kidneys were preserved in 1 of 3 settings: normothermic whole blood (NT-WB), normothermic Steen Solution™ (XVIVO Perfusion) with whole blood (NT-Steen/WB), or subnormothermic Steen Solution™ at 21°C (SNT-Steen)...
June 9, 2017: International Journal of Artificial Organs
Philip C May, Wayne Kreider, Adam D Maxwell, Yak-Nam Wang, Bryan W Cunitz, Philip M Blomgren, Cynthia D Johnson, Joshua S H Park, Michael R Bailey, Donghoon Lee, Jonathan D Harper, Mathew D Sorensen
PURPOSE: Burst wave lithotripsy (BWL) is a transcutaneous technique with potential to safely and effectively fragment renal stones. Preclinical investigations of BWL require the assessment of potential renal injury. This study evaluates the capabilities of real-time ultrasound and MRI to detect and evaluate BWL injury that was induced in porcine kidneys. MATERIALS AND METHODS: Ten kidneys from five female farm pigs were treated with either a 170 or 335 kHz BWL transducer using variable treatment parameters and monitored in real-time with ultrasound...
August 2017: Journal of Endourology
J Moritz Kaths, Andreas Paul, Lisa A Robinson, Markus Selzner
Kidney transplantation is the treatment of choice for end-stage renal disease. Despite its superiority over dialysis, the persisting organ shortage remains a major drawback. Additional sources to increase the donor pool are grafts recovered from extended criteria donors (ECD) and donation after circulatory death (DCD). Although transplantation of marginal grafts demonstrates promising outcomes, increased rates of primary non-function, delayed graft function, and reduced graft survival have been reported. Cold ischemic injury, caused by static cold storage is a significant risk factor for poor outcome...
January 2018: Transplantation Reviews
David K C Cooper
Dr Thomas E. Starzl, who died on March 4, 2017, was one of the great pioneers of organ transplantation. He was also a pioneer in the field of xenotransplantation. In 1964, he carried out baboon kidney transplants in six patients with terminal renal disease for whom no living or deceased donor became available; graft survival was for 19-60 days, the grafts being lost largely through continuous complement activation. Between 1966 and 1974, he carried out one ex vivo liver perfusion and three orthotopic liver transplants using chimpanzees as sources of organs; graft survival was for <14 days...
March 2017: Xenotransplantation
J M Kaths, J Echeverri, I Linares, J Y Cen, S Ganesh, M Hamar, P Urbanellis, P Yip, R John, D Bagli, I Mucsi, A Ghanekar, D Grant, L A Robinson, M Selzner
Normothermic ex vivo kidney perfusion (NEVKP) demonstrated superior results compared to hypothermic storage in donation after circulatory death (DCD) kidney transplantation. It is unknown whether an optimal perfusion time exists following hypothermic storage to allow for the recovery of renal grafts from cold ischemic injury. In a porcine model of DCD kidney autotransplantation, the impact of initial static cold storage (SCS) (8 h) followed by various periods of NEVKP recovery was investigated: group A, 8 hSCS only (control); group B, 8 hSCS + 1 hNEVKP (brief NEVKP); group C, 8 hSCS + 8 hNEVKP (intermediate NEVKP); and group D, 8 hSCS + 16 hNEVKP (prolonged NEVKP)...
April 4, 2017: American Journal of Transplantation
Kamil Kus, Edyta Kus, Agnieszka Zakrzewska, Wojciech Jawien, Barbara Sitek, Maria Walczak, Stefan Chlopicki
PURPOSE: To analyze the effect of liver steatosis and obesity on pharmacokinetic profile of two structurally-related liver-selective NO-donors - V-PYRRO/NO and V-PROLI/NO. METHODS: C57BL/6 mice were fed control or high-fat diet for 15 weeks to induced liver steatosis and obesity (HFD mice). Pharmacokinetics and renal elimination studies were conducted in vivo following iv dosing of V-PYRRO/NO and V-PROLI/NO (0.03mmol/kg). Hepatic clearance was evaluated ex vivo in the isolated perfused mice liver and in vitro with the use of liver microsomes...
June 2017: Pharmacological Reports: PR
Thomas D Adams, Meeta Patel, Sarah A Hosgood, Michael L Nicholson
BACKGROUND: Ex vivo perfusion (EVP) is a novel method of preservation. However, optimal perfusion conditions remain undetermined. Reducing the temperature of the perfusate to subnormothermia may be beneficial during EVP and improve early graft function. The aim of this study was to investigate whether subnormothermia would influence the conditioning effect of EVP when compared with normothermic perfusion, and standard cold static storage (CS). METHODS: Porcine kidneys underwent static CS for 23 hours followed by 1 hour of EVP using leukocyte-depleted blood at a mean temperature of 32°C or 37°C...
March 2017: Transplantation Direct
Chung-Kan Peng, Kun-Lun Huang, Chou-Chin Lan, Yu-Juei Hsu, Geng-Chin Wu, Chia-Hui Peng, Chin-Pyng Wu, Khee-Siang Chan
Lung ischemia reperfusion injury (LIRI) is one of important complications following lung transplant and cardiopulmonary bypass. Although patients on hemodialysis are still excluded as lung transplant donors because of the possible effects of renal failure on the lungs, increased organ demand has led us to evaluate the influence of chronic kidney disease (CKD) on LIRI. A CKD model was induced by feeding Sprague-Dawley rats an adenine-rich (0.75%) diet for 2, 4 and 6 weeks, and an isolated rat lung in situ model was used to evaluate ischemia reperfusion (IR)-induced acute lung injury...
2017: PloS One
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