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531 results on '"Uygun, Korkut"'

151. Nuclear receptors control pro-viral and antiviral metabolic responses to hepatitis C virus infection

Author

Levy, Gahl, primary, Habib, Naomi, additional, Guzzardi, Maria Angela, additional, Kitsberg, Daniel, additional, Bomze, David, additional, Ezra, Elishai, additional, Uygun, Basak E, additional, Uygun, Korkut, additional, Trippler, Martin, additional, Schlaak, Joerg F, additional, Shibolet, Oren, additional, Sklan, Ella H, additional, Cohen, Merav, additional, Timm, Joerg, additional, Friedman, Nir, additional, and Nahmias, Yaakov, additional

Published
2016
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152. Ex Situ Normothermic Machine Perfusion of Donor Livers

Author

Karimian, Negin, Matton, Alix P.M., Westerkamp, Andrie C., Burlage, Laura C., op den Dries, Sanna, Leuvenink, Henri G.D., Lisman, Ton, Uygun, Korkut, Markmann, James F., Porte, Robert J., Groningen Institute for Organ Transplantation (GIOT), and Vascular Ageing Programme (VAP)

Subjects
Cryopreservation, Male, Issue 99, Machine perfusion, liver transplantation, BILIARY COMPLICATIONS, TRANSPLANTATION, preservation, normothermic, Organ Preservation, Middle Aged, Tissue Donors, Oxygen, Perfusion, Liver, RISK-FACTORS, INJURY, Humans, Medicine, REPERFUSION, GRAFTS, hypothermic, STRICTURES, human donor liver
Abstract

In contrast to conventional static cold preservation (0-4 degrees C), ex situ machine perfusion may provide better preservation of donor livers. Continuous perfusion of organs provides the opportunity to improve organ quality and allows ex situ viability assessment of donor livers prior to transplantation. This video article provides a step by step protocol for ex situ normothermic machine perfusion (37 degrees C) of human donor livers using a device that provides a pressure and temperature controlled pulsatile perfusion of the hepatic artery and continuous perfusion of the portal vein. The perfusion fluid is oxygenated by two hollow fiber membrane oxygenators and the temperature can be regulated between 10 degrees C and 37 degrees C. During perfusion, the metabolic activity of the liver as well as the degree of injury can be assessed by biochemical analysis of samples taken from the perfusion fluid. Machine perfusion is a very promising tool to increase the number of livers that are suitable for transplantation.

Published
2015

153. Supercooling Preservation Of The Rat Liver For Transplantation

Author

Bruinsma, Bote G., Berendsen, Tim A., Izamis, Maria-Louisa, Yeh, Heidi, Yarmush, Martin L., and Uygun, Korkut

Subjects
Cryopreservation, Cryoprotective Agents, Liver, Animals, Organ Preservation, Article, Liver Transplantation, Rats
Abstract

The current standard for liver preservation involves cooling of the organ on ice (0-4 °C). Although it is successful for shorter durations, this method of preservation does not allow long-term storage of the liver. The gradual loss of hepatic viability during preservation puts pressure on organ sharing and allocation, may limit the use of suboptimal grafts and necessitates rushed transplantation to achieve desirable post-transplantation outcomes. In an attempt to improve and prolong liver viability during storage, alternative preservation methods are under investigation. For instance, ex vivo machine perfusion systems aim to sustain and even improve viability by supporting hepatic function at warm temperatures, rather than simply slowing down deterioration by cooling. Here we describe a novel subzero preservation technique that combines ex vivo machine perfusion with cryoprotectants to facilitate long-term supercooled preservation. The technique improves the preservation of rat livers to prolong storage times as much as threefold, which is validated by successful long-term recipient survival after orthotopic transplantation. This protocol describes how to load rat livers with cryoprotectants to prevent both intracellular and extracellular ice formation and to protect against hypothermic injury. Cryoprotectants are loaded ex vivo using subnormothermic machine perfusion (SNMP), after which livers can be cooled to -6 °C without freezing and kept viable for up to 96 h. Cooling to a supercooled state is controlled, followed by 3 h of SNMP recovery and orthotopic liver transplantation.

Published
2015

155. Abstract

Author

Lellouch, Alexandre G., primary, Karimian, Negin, additional, Yang Ng, Zhi, additional, Mert, Safak, additional, Geerts, Sharon, additional, Uygun, Korkut, additional, and Cetrulo, Curtis L., additional

Published
2016
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157. Bulk Droplet Vitrification: An Approach to Improve Large-Scale Hepatocyte Cryopreservation Outcome

Author

de Vries, Reinier J., Banik, Peony D., Nagpal, Sonal, Weng, Lindong, Ozer, Sinan, van Gulik, Thomas M., Toner, Mehmet, Tessier, Shannon N., and Uygun, Korkut

Abstract

Loss of hepatocyte viability and metabolic function after cryopreservation is still a major issue. Although vitrification is a promising alternative, it has generally been proven to be unsuitable for vitrification of large cell volumes which is required for clinical applications. Here, we propose a novel bulk droplet (3–5 mm diameter) vitrification method which allows high throughput volumes (4 mL/min), while using a low preincubated CPA concentration (15% v/v) to minimize toxicity and loss of cell viability and function. We used rapid (1.25 s) osmotic dehydration to concentrate a low preincubated intracellular CPA concentration ahead of vitrification, without the need of fully equilibrating toxic CPA concentrations. We compared direct postpreservation viability, long-term viability, and metabolic function of bulk droplet vitrified, cryopreserved, and fresh hepatocytes. Simulations and cooling rate measurements confirmed an adequate concentration of the intracellular CPA concentration (up to 8.53 M) after dehydration in combination with high cooling rates (960–1320 °C/min) for successful vitrification. In comparison to cryopreserved hepatocytes, bulk droplet vitrified hepatocytes had a significantly higher viability, directly after preservation and after 1 day in culture. Moreover, bulk droplet vitrified hepatocytes had evidently better morphology and showed significantly higher metabolic activity than cryopreserved hepatocytes in long-term collagen sandwich cultures. In conclusion, we developed a novel bulk droplet vitrification method of which we validated the theoretical background and demonstrated the feasibility to use this method to vitrify large cell volumes. Moreover, we showed that this method results in improved hepatocyte viability and metabolic function as compared to cryopreservation.

Published
2019
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158. Methods in Bioengineering: Organ Preservation and Reengineering

Author

Uygun, Korkut, Lee, Charles Y., Uygun, Korkut, and Lee, Charles Y.

Subjects
Preservation of organs, tissues, etc.--Methodology, Bioengineering--Methodology
Abstract

'Written and edited by recognized experts in the field, the new Artech House Methods in Bioengineering book series offers detailed guidance on authoritative methods for addressing specific bioengineering challenges. Offering a highly practical presentation of each topic, each book provides research engineers, scientists, and students with step-by-step procedures, clear examples, and effective ways to overcome problems that may be encountered. This first-of-its-kind volume addresses the important challenge of organ preservation and reengineering. The book presents cutting-edge techniques for damaged livers and hearts via normothermic perfusion, hypothermic machine perfusion for the liver, kidney and pancreas, and imaging techniques to assess the viability of injured kidneys. Professionals and researchers also find methods to decellularize whole organs to create scaffolds for tissue engineering. Moreover, the book presents an approach to enhancing hepatocyte recovery from marginal livers.'

Published
2011

165. Injury to peribiliary glands and vascular plexus before liver transplantation predicts formation of non-anastomotic biliary strictures

Author

op den Dries, Sanna, primary, Westerkamp, Andrie C., additional, Karimian, Negin, additional, Gouw, Annette S.H., additional, Bruinsma, Bote G., additional, Markmann, James F., additional, Lisman, Ton, additional, Yeh, Heidi, additional, Uygun, Korkut, additional, Martins, Paulo N., additional, and Porte, Robert J., additional

Published
2014
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170. Whole liver engineering

Author

Uygun, Basak E., primary, Kim, Yeonhee, additional, Berendsen, Tim, additional, Ozer, Sinan, additional, Yarmush, Martin L., additional, and Uygun, Korkut, additional

Published
2012
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176. Role of Machine Perfusion in Liver Transplantation.

Author

Longchamp, Alban, Nakamura, Tsukasa, Uygun, Korkut, and Markmann, James F.

Abstract

Given the current severe shortage of available livers for transplantation, there is an urgent need to maximize the utilization of donor organs. One of the strategies to increase the number of available livers for transplantation is to improve organ utilization through the use of elderly, overweight, or organs donated after circulatory death (DCD). However, the utilization of these “marginal” organs was associated with an increased risk of early allograft dysfunction, primary non-function, ischemic biliary complications or even re-transplantation. Ischemia–reperfusion (IR) injury is a key mechanism in the pathogenesis of these complication. Although conventional static cold preservation provides some protection against IR injury, more-advanced preservation methods are needed to improve outcomes after transplantation of marginal livers or obtained after circulatory death. Among the most promising strategies is the utilization of ex-vivo machine perfusion. Recently, a variety of perfusion machines have received approval for clinical use, each differing in terms of perfusion temperature and oxygenation capabilities. Overall, clinical trials have demonstrated that these devices have resulted in superior posttransplant outcomes and increased utilization of marginal livers, leading to their widespread adoption. In this review, we aim to provide both the rationale and up-to-date clinical evidence for machine perfusion, along with its potential future applications.

Published
2023
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193. Subnormothermic Ex Vivo Porcine Kidney Perfusion Improves Energy Metabolism: Analysis Using 31P Magnetic Resonance Spectroscopic Imaging

Author

Agius, Thomas, Songeon, Julien, Klauser, Antoine, Allagnat, Florent, Longchamp, Grégoire, Ruttimann, Raphael, Lyon, Arnaud, Ivaniesevic, Julijana, Meier, Raphael, Déglise, Sébastien, Markmann, James F., Uygun, Korkut, Buhler, Leo, Toso, Christian, Corpataux, Jean-Marc, Lazeyras, Francois, and Longchamp, Alban

Published
2022
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197. A novel 3D liver organoid system for elucidation of hepatic glucose metabolism.

Author

Lu, Yanhua, Zhang, Guoliang, Shen, Chong, Uygun, Korkut, Yarmush, Martin L., and Meng, Qin

Abstract

Hepatic glucose metabolism is a key player in diseases such as obesity and diabetes as well as in antihyperglycemic drugs screening. Hepatocytes culture in two-dimensional configurations is limited in vitro model for hepatocytes to function properly, while truly practical platforms to perform three-dimensional (3D) culture are unavailable. In this work, we present a practical organoid culture method of hepatocytes for elucidation of glucose metabolism under nominal and stress conditions. Employing this new method of culturing cells within a hollow fiber reactor, hepatocytes were observed to self-assemble into 3D spherical organoids with preservation of tight junctions and display increased liver-specific functions. Compared to both monolayer culture and sandwich culture, the hepatocyte organoids displayed higher intracellular glycogen content, glucose consumption, and gluconeogenesis and approached the in vivo values, as also confirmed by gene expression of key enzymes. Moreover, hepatocyte organoids demonstrated more realistic sensitivity to hormonal challenges with insulin, glucagon, and dexamethasone. Finally, the exposure to high glucose demonstrated toxicities including alteration of mitochondrial membrane potential, lipid accumulation, and reactive oxygen species formation, similar to the in vivo responses, which was not captured by monolayer cultures. Collectively, hepatocyte organoids mimicked the in vivo functions better than hepatocyte monolayer and sandwich cultures, suggesting suitability for applications such as antihyperglycemic drugs screening. Biotechnol. Bioeng. 2012; 109:595-604. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Published
2012
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198. In situ metabolic flux analysis to quantify the liver metabolic response to experimental burn injury.

Author

Izamis, Maria-Louisa, Sharma, Nripen S., Uygun, Basak, Bieganski, Robert, Saeidi, Nima, Nahmias, Yaakov, Uygun, Korkut, Yarmush, Martin L., and Berthiaume, Francois

Subjects
LIVER injuries, METABOLISM, GLUCONEOGENESIS, GLYCOLYSIS, GLUCOSE synthesis
Abstract

The article presents a study that investigated the liver's metabolic state in response to trauma. The study involved laboratory rats where one control group was uninjured, another set had 20% total body surface area (TBSA) scald burn, and the third group 40% TBSA scald burn. All underwent hypermetabolic response and were forced to fast one day prior to evaluation. Results revealed that controls exhibited gluconeogenic patterns of fasting, the 20%TBSA burn group presented glycolytic-like features, and 40% TBSA burn exhibited increased gluconeogenesis.

Published
2011
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199. PROCESS SECURITY IN ChE EDUCATION.

Author

Piluso, Cristina, Uygun, Korkut, Huang, Yinlun, and Lou, Helen H.

Subjects
CHEMICAL engineering, CHEMICAL processes, INDUSTRIAL arts, ENGINEERING, SAFETY
Abstract

Discusses the value and necessity of a process-security concept in undergraduate chemical engineering curriculum, as an addition to or extension of the existing process safety material. Importance of process safety to the chemical process industry; Process security evaluation methodology; Integration of process security into senior design; Software used in the instruction of process security.

Published
2005

200. Two‐day Static Cold Preservation of α1,3‐Galactosyltransferase Knockout Kidney Grafts Before Simulated Xenotransplantation.

Author

Mojoudi, Mohammadreza, Taggart, McLean, Karadagi, Ahmad, Hassan, Madeeha, Tomosugi, Toshihide, Tomofuji, Katsuhiro, Agius, Thomas, Lyon, Arnaud, Nakamura, Tsukasa, Taveras, Christopher, Ozgur, Ozge Sila, Kharga, Anil, Matheson, Rudy, Riella, Leonardo V., Kimura, Shoko, Yeh, Heidi, Markmann, James F., Kawai, Tatsuo, Uygun, Korkut, and Longchamp, Alban

Abstract

Transplantation remains the preferred treatment for end‐stage kidney disease but is critically limited by the number of available organs. Xenografts from genetically modified pigs have become a promising solution to the loss of life while waiting for transplantation. However, the current clinical model for xenotransplantation will require off‐site procurement, leading to a period of ischemia during transportation. As of today, there is limited understanding regarding the preservation of these organs, including the duration of viability, and the associated molecular changes. Thus, our aim was to evaluate the effects of static cold storage (SCS) on α1,3‐galactosyltransferase knockout (GGTA1 KO) kidney. After SCS, viability was further assessed using acellular sub‐normothermic ex vivo perfusion and simulated transplantation with human blood. Compared to baseline, tubular and glomerular interstitium was preserved after 2 days of SCS in both WT and GGTA1 KO kidneys. Bulk RNA‐sequencing demonstrated that only eight genes were differentially expressed after SCS in GGTA1 KO kidneys. During sub‐normothermic perfusion, kidney function, reflected by oxygen consumption, urine output, and lactate production was adequate in GGTA1 KO grafts. During a simulated transplant with human blood, macroscopic and histological assessment revealed minimal kidney injury. However, GGTA1 KO kidneys exhibited higher arterial resistance, increased lactate production, and reduced oxygen consumption during the simulated transplant. In summary, our study suggests that SCS is feasible for the preservation of porcine GGTA1 KO kidneys. However, alternative preservation methods should be evaluated for extended preservation of porcine grafts. [ABSTRACT FROM AUTHOR]

Published
2024
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