Article
Surgery
Emily R. Thompson, Avinash Sewpaul, Rodrigo Figuereido, Lucy Bates, Samuel J. Tingle, John R. Ferdinand, Gerhard R. Situmorang, Shameem S. Ladak, Chloe M. Connelly, Sarah A. Hosgood, Michael L. Nicholson, Menna R. Clatworthy, Simi Ali, Colin H. Wilson, Neil S. Sheerin
Summary: Normothermic machine perfusion (NMP) is a novel clinical approach used to evaluate and repair organs. This study reports the delivery of oligonucleotide-based therapy to human kidneys during NMP, demonstrating the potential of NMP to bind and block detrimental microRNAs in donor kidneys prior to transplantation.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Surgery
Dinesh Jaishankar, Kristen M. Quinn, Jes Sanders, Leah Plumblee, Thomas A. Morinelli, Satish N. Nadig
Summary: This article discusses the regulatory influence of connexin proteins in maintaining endothelial cell barrier integrity and their role in ischemia-reperfusion injury in organ transplantation. Certain isoforms of connexin proteins play a crucial role in preserving organ function, but more research is needed to understand their roles in transplant immunology and their application in targeted therapeutics.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Medicine, General & Internal
Sara Akalay, Sarah A. Hosgood
Summary: Although machine perfusion is gradually being applied in clinical practice, the improvement of organ reconditioning therapies is still at the experimental stage, showing a translational gap. This review discusses the biological processes and current strategies and interventions for preventing ischemia-reperfusion injury, treating its deleterious consequences, or supporting the reparative response of the kidney, and explores prospects to improve the clinical translation of these therapies by addressing multiple aspects of ischemia-reperfusion injury to achieve robust and long-lasting protective effects on the kidney graft.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Surgery
Stine Lohmann, Merel B. F. Pool, Kaithlyn M. Rozenberg, Anna K. Keller, Cyril Moers, Ulla Moldrup, Bjarne K. Moller, Stina J. M. Lignell, Soren Krag, Jesus M. Sierra-Parraga, Maria L. Lo Faro, James Hunter, Martin J. Hoogduijn, Carla C. Baan, Henri G. D. Leuvenink, Rutger J. Ploeg, Marco Eijken, Bente Jespersen
Summary: This study aimed to evaluate the safety and feasibility of using MSC treatment during NMP in a porcine autotransplantation model, and found that infusing MSCs during ex vivo NMP of porcine kidneys was safe and feasible. However, no beneficial effects of ex vivo MSC therapy could be demonstrated during the short posttransplant follow-up period of 14 days.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Review
Immunology
Jiale Li, Qinbao Peng, Ronghua Yang, Kunsheng Li, Peng Zhu, Yufeng Zhu, Pengyu Zhou, Gabor Szabo, Shaoyi Zheng
Summary: This review discusses the use of machine perfusion and mesenchymal stem cells to improve the quality and outcomes of marginal organs in transplantation. By continuously perfusing the organs to mimic physiological conditions, evaluating pre-transplant organ function, and treating the organs with pharmacological, gene, and stem cell therapy, the quality and adaptability of the organs can be enhanced. Promising preclinical results indicate the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.
FRONTIERS IN IMMUNOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Hanno Maassen, Leonie H. Venema, Marc G. Weiss, Tobias M. Huijink, H. Sijbrand Hofker, Anna K. Keller, Tom E. Mollnes, Marco Eijken, Soren E. Pischke, Bente Jespersen, Harry van Goor, Henri G. D. Leuvenink
Summary: Kidney extraction time has a detrimental effect on post-transplantation outcome. This study aimed to improve the flush-out and decrease ischemic injury by adding hydrogen sulphide (H2S) to the flush medium. The addition of H2S during flush out and static cold storage resulted in a reduction in pro-inflammatory cytokines without affecting renal function or injury markers.
Review
Medicine, General & Internal
Julie De Beule, Delphine Keppens, Hannelie Korf, Ina Jochmans
Summary: There is uncertainty about the composition of the perfusate for normothermic kidney perfusion, and the effect of different perfusate components or ischemic conditions on cytokine levels is unclear. Further research is needed to understand the role of leukocyte filters and the changes in cytokine levels during different ischemic conditions.
JOURNAL OF CLINICAL MEDICINE
(2022)
Article
Surgery
Kai Nishime, Chika Miyagi-Shiohira, Kazuho Kuwae, Yoshihito Tamaki, Tasuku Yonaha, Mayuko Sakai-Yonaha, Issei Saitoh, Masami Watanabe, Hirofumi Noguchi
Summary: Hydrogen sulfide can protect organ grafts against ischemia-reperfusion injury, leading to improved success rates of islet transplantation. Preservation of pancreas in UW solution supplemented with AP39 can protect pancreatic islets against IRI and enhance islet transplantation outcomes.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Surgery
Yue Hou, Yanbao Xin, Shuhan Liu, Yong Li, Xiandi Meng, Jialiang Wang, Zhonggao Xu, Tianmeng Sun, Yong-Guang Yang
Summary: In this study, a nanotechnology-based therapy targeting TSP-1 was developed to prevent renal ischemia-reperfusion injury (IRI). The biocompatible nanoparticles effectively adsorbed and neutralized TSP-1, providing strong protection against renal IRI.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Review
Pharmacology & Pharmacy
Min Cao, Guoqing Wang, Hongli He, Ruiming Yue, Yong Zhao, Lingai Pan, Weiwei Huang, Yang Guo, Tao Yin, Lina Ma, Dingding Zhang, Xiaobo Huang
Summary: The transplant community is still striving to improve graft quality and recipient prognosis, with a focus on enhancing oxygenation during organ preservation. The addition of HBOCs to traditional preservation protocols has shown promise in providing more oxygen to organs, reducing ischemia-reperfusion injury, and increasing the pool of transplantable donors.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cardiac & Cardiovascular Systems
Etienne Abdelnour-Berchtold, Aadil Ali, Cristina Baciu, Erika L. Beroncal, Aizhou Wang, Olivia Hough, Mitsuaki Kawashima, Manyin Chen, Yu Zhang, Mingyao Liu, Tom Waddell, Ana C. Andreazza, Shaf Keshavjee, Marcelo Cypel
Summary: Injured donor lungs stored at 10℃ demonstrated superior oxygenation and protective effects compared to the current clinical standard of 4℃ storage.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Biochemistry & Molecular Biology
Adam Hosszu, Akos R. R. Toth, Tamas Lakat, Ganna Stepanova, Zsuzsanna Antal, Laszlo J. J. Wagner, Attila J. J. Szabo, Andrea Fekete
Summary: Kidney transplantation is the preferred treatment for end-stage kidney disease, and optimizing organ condition is crucial due to the shortage of transplantable organs. This study demonstrated that supplementing the preservation solution with the S1R agonist fluvoxamine reduced cold and warm ischemic injury, improved kidney function, mitigated histological injury, and reduced inflammation. The results suggest that S1R agonists have great potential in improving organ preservation and alleviating the problem of organ shortages.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Laura Zarnitz, Benedict M. Doorschodt, Lisa Ernst, Aisa Hosseinnejad, Eileen Edgworth, Tamara Fechter, Alexander Theissen, Sonja Djudjaj, Peter Boor, Rolf Rossaint, Rene H. Tolba, Christian Bleilevens
Summary: Donor organ shortage has led to the use of marginal grafts, but normothermic machine perfusion (NMP) can assess and restore the viability of these grafts before transplantation. An alternative to autologous packed red blood cell (pRBC)-based perfusates is the cell- and oxygen carrier-free solution Ecosol, supplemented with taurine, which may prevent adverse effects. This study compared the effects of 6 h NMP using pRBC and Ecosol on porcine kidneys, and found that despite some tissue damage in the Ecosol group, functional parameters and oxygenation were similar to the pRBC group, and taurine improved antioxidant capacity in the Ecosol group.
Article
Biochemistry & Molecular Biology
Eileen Edgworth, Lisa Ernst, Zoltan Czigany, Turgay Saritas, Laura Sophie Zarnitz, Marc Wiartalla, Peter Boor, Eva Miriam Buhl, Rolf Rossaint, Rene H. Tolba, Benedict Doorschodt, Gregor Fabry, Christian Bleilevens
Summary: Normothermic machine perfusion (NMP) combined with optimized perfusate composition can improve the quality of kidney preservation, but the optimization of perfusates is still under research. Hemoglobin-based oxygen carriers (HBOCs), such as HBOC-301, can be an alternative to packed red blood cells (pRBC), but they can cause methemoglobin formation and induce hypoxia. The addition of ascorbic acid (VitC) as an antioxidant may have a beneficial effect. This study showed that HBOC-301 is inferior to pRBCs in a porcine kidney NMP model, regardless of the addition of VitC. Oxidative stress and fragmentation of hemoglobin polymers may contribute to these results, indicating the need for further research on cell-free oxygen carriers without these issues.
Review
Cell Biology
Marc Mico-Carnero, Mohamed Amine Zaouali, Carlos Rojano-Alfonso, Cristina Maroto-Serrat, Hassen Ben Abdennebi, Carmen Peralta
Summary: Ischemia and reperfusion injury (IRI), an inevitable step in organ transplantation, can cause serious organ damage. Most organs used for transplantation today come from extended criteria donors (ECDs), which are more sensitive to IRI. The main objective of organ preservation solutions is to protect against IRI through specific components.
Article
Nanoscience & Nanotechnology
Gregory T. Tietjen, Jenna DiRito, Jordan S. Pober, W. Mark Saltzman
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
(2017)
Article
Cell Biology
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
SCIENCE TRANSLATIONAL MEDICINE
(2017)
Article
Chemistry, Multidisciplinary
Jiajia Cui, Alexandra S. Piotrowski-Daspit, Junwei Zhang, Mingjie Shao, Laura G. Bracaglia, Teruo Utsumi, Young-Eun Seo, Jenna DiRito, Eric Song, Christine Wu, Asuka Inadab, Gregory T. Tietjen, Jordan S. Pober, Yasuko Iwakiri, W. Mark Saltzman
JOURNAL OF CONTROLLED RELEASE
(2019)
Article
Surgery
Jenna R. DiRito, Sarah A. Hosgood, Melanie Reschke, Claire Albert, Laura G. Bracaglia, John R. Ferdinand, Benjamin J. Stewart, Christopher M. Edwards, Anand G. Vaish, Sathia Thiru, David C. Mulligan, Danielle J. Haakinson, Menna R. Clatworthy, W. Mark Saltzman, Jordan S. Pober, Michael L. Nicholson, Gregory T. Tietjen
Summary: The study reveals a new mechanism of injury in marginal organs during cold storage, and suggests that normothermic machine perfusion combined with plasminogen and tissue plasminogen activator can improve organ conditions and has potential for translational benefits.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Article
Multidisciplinary Sciences
Valerie L. Luks, Hanna Mandl, Jenna DiRito, Christina Barone, Mollie R. Freedman-Weiss, Adele S. Ricciardi, Gregory G. Tietjen, Marie E. Egan, W. Mark Saltzman, David H. Stitelman
Summary: This study demonstrates the enhanced nanoparticle uptake in epithelial cells by conjugating target-specific antibodies onto the nanoparticle surface, potentially improving the efficacy of genetic disease treatment.