Review
Immunology
Maximilian J. Roesel, Nirmal S. Sharma, Andreas Schroeter, Tomohisa Matsunaga, Yao Xiao, Hao Zhou, Stefan G. Tullius
Summary: Transplant centers use older donors to meet the demand for lung transplantation, but this is associated with a higher rate of lung ischemia reperfusion injury. Understanding and improving the condition of older lungs is critical to optimize transplant outcomes. Ex vivo lung perfusion can recondition ischemic lungs through ex-vivo perfusing and ventilation.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Medicine, Research & Experimental
Mingchu Sun, Wenhua Jiang, Nan Mu, Zihui Zhang, Lu Yu, Heng Ma
Summary: Cardiovascular disease (CVD) is the leading cause of noncommunicable disease-related death worldwide, and effective therapeutic strategies against CVD are urgently needed. Mitochondria dysfunction involves in the onset and development of CVD. Nowadays, mitochondrial transplantation, an alternative treatment aimed at increasing mitochondrial number and improving mitochondrial function, has been emerged with great therapeutic potential. Substantial evidence indicates that mitochondrial transplantation improves cardiac function and outcomes in patients with CVD. Therefore, mitochondrial transplantation has profound implications in the prevention and treatment of CVD.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Cell Biology
Toyofumi Fengshi Chen-Yoshikawa
Summary: Lung transplantation is an established treatment for end-stage respiratory failure, but ischemia-reperfusion injury (IRI) remains a significant complication. The pathophysiology of lung IRI is not fully understood, but promising therapeutic strategies such as the ex vivo lung perfusion system are being developed to improve outcomes.
Article
Cell Biology
Jan Van Slambrouck, Dirk Van Raemdonck, Robin Vos, Cedric Vanluyten, Arno Vanstapel, Elena Prisciandaro, Lynn Willems, Michaela Orlitova, Janne Kaes, Xin Jin, Yanina Jansen, Geert M. Verleden, Arne P. Neyrinck, Bart M. Vanaudenaerde, Laurens J. Ceulemans
Summary: Primary graft dysfunction (PGD) is the clinical syndrome of acute lung injury after lung transplantation, involving various levels including clinical, physiological, radiological, histological, and cellular. Understanding these aspects of PGD can provide insights into acute lung failure after transplantation and contribute to the development of novel therapies.
Article
Cell Biology
Fiorella Calabrese, Federica Pezzuto, Francesco Fortarezza, Francesca Lunardi, Eleonora Faccioli, Giulia Lorenzoni, Annalisa Boscolo, Nicolo Sella, Dario Gregori, Marco Schiavon, Paolo Navalesi, Andrea Dell'Amore, Federico Rea
Summary: This study investigated tissue/molecular pathways and tissue injury in lung transplantation recipients supported by intraoperative VA-ECMO. The findings suggest lower lung tissue injury and decreased leukocyte margination in the ECMO group compared to the non-ECMO group.
Article
Multidisciplinary Sciences
Wenjun Li, Yuriko Terada, Yulia Y. Tyurina, Vladimir A. Tyurin, Amit Bery, Jason M. Gauthier, Ryuji Higashikubo, Alice Y. Tong, Dequan Zhou, Felix Nunez-Santana, Emilia Lecuona, Adil Hassan, Kohei Hashimoto, Davide Scozzi, Varun Puri, Ruben G. Nava, Alexander S. Krupnick, Kory J. Lavine, Andrew E. Gelman, Mark J. Miller, Valerian E. Kagan, Ankit Bharat, Daniel Kreisel
Summary: Ischemia reperfusion injury is a common pathological condition triggered by the release of endogenous ligands. In this study, the researchers discovered that necroptosis, a nonapoptotic form of cell death, triggers the recruitment of neutrophils in injured lungs. Initially, neutrophils traffic predominantly to subpleural vessels, guided by chemoattractants produced by nonclassical monocytes. The disruption of pulmonary capillaries by neutrophils leads to vascular leakage and impaired graft function. The study also found that TLR4 signaling and NADPH oxidase 4 expression mediate the arrest of neutrophils, preventing their extravasation. The formation of neutrophil extracellular traps in injured lungs can be disrupted with DNase to prevent vascular leakage and improve graft dysfunction. These findings could have important implications for the development of therapeutics to protect lungs from ischemia reperfusion injury.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cardiac & Cardiovascular Systems
Rongjun Zou, Wanting Shi, Junxiong Qiu, Na Zhou, Na Du, Hao Zhou, Xinxin Chen, Li Ma
Summary: Empagliflozin can protect microvasculature during myocardial ischemia reperfusion injury (I/R) by inhibiting the DNA-PKcs/Fis1/mitochondrial fission pathway.
CARDIOVASCULAR DIABETOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Caryn M. Cloer, Christopher S. Givens, Lakisha K. Buie, Lauren K. Rochelle, Yi-Tzu Lin, Sam Popa, Randolph V. M. Shelton, James Zhan, Tyler R. Zimmerman, Bria G. Jones, Zion Lesesne, Sarah S. Hogan, Thomas H. Petersen
Summary: A study found that freezing and injecting allogeneic mitochondria into damaged lung tissue can reduce graft rejection caused by ischemia-reperfusion injury during lung transplantation. The transplanted mitochondria induce autophagy and improve lung function through anti-inflammatory and antioxidant effects. The results provide new insights into the therapeutic potential of mitochondrial transplant to alleviate ischemia-reperfusion injury during lung transplant.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Cardiac & Cardiovascular Systems
Lillian Benck, P. Evan Kransdorf, A. Dominic Emerson, Joshua Rushakoff, M. Michelle Kittleson, B. Ellen Klapper, J. Dominick Megna, Fardad Esmailian, Chelsea Halprin, Alfredo Trento, Danny Ramzy, S. C. Lawrence Czer, H. David Chang, E. Joseph Ebinger, A. Jon Kobashigawa, K. Jignesh Patel
Summary: The study identified recipient, donor, and surgical risk factors associated with severe primary graft dysfunction (PGD) following heart transplant, and developed a clinical risk score (ABCE) that showed good discrimination and calibration for severe PGD. Further research into the underlying mechanisms of PGD development is urgently needed to better understand the differing pathophysiology of mild/moderate and severe PGD.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2021)
Review
Surgery
Jasper Iske, Christopher A. Hinze, Jawad Salman, Axel Haverich, Stefan G. Tullius, Fabio Ius
Summary: Allogeneic lung transplantation is the treatment of choice for advanced lung diseases, but ischemia reperfusion injury remains a crucial issue during the transplant process. Ex vivo lung perfusion technique can reduce the incidence of primary graft dysfunction and improve organ quality.
AMERICAN JOURNAL OF TRANSPLANTATION
(2021)
Review
Cell Biology
Keir A. Forgie, Nicholas Fialka, Darren H. Freed, Jayan Nagendran
Summary: Lung transplantation is the gold standard treatment for end-stage lung disease, but waitlist mortality is high due to a shortage of suitable donor lungs. Lung ischemic reperfusion injury (LIRI) can compromise organ quality and lead to primary graft dysfunction (PGD). Research into preservation strategies to decrease the risk of LIRI and PGD is crucial for improving patient outcomes.
Review
Medicine, Research & Experimental
Kei Hayashida, Ryosuke Takegawa, Muhammad Shoaib, Tomoaki Aoki, Rishabh C. Choudhary, Cyrus E. Kuschner, Mitsuaki Nishikimi, Santiago J. Miyara, Daniel M. Rolston, Sara Guevara, Junhwan Kim, Koichiro Shinozaki, Ernesto P. Molmenti, Lance B. Becker
Summary: This systematic review examined animal and human studies on ischemia reperfusion injury (IRI) and found evidence supporting the potential beneficial effects of mitochondrial transplantation. However, clinical translation of this approach remains limited, highlighting the need for further investigations into mechanisms of action and patient outcomes.
JOURNAL OF TRANSLATIONAL MEDICINE
(2021)
Review
Pharmacology & Pharmacy
Yuanbo Qi, Mingyao Hu, Zhigang Wang, Wenjun Shang
Summary: The injury caused by ischemia and reperfusion during kidney transplantation remains unsatisfactory. Iron plays a pathological role in tissue damage induced by I/R, but the effects of iron-related therapy are controversial. Mitochondria regulate iron homeostasis and contribute to I/R injury development. The understanding of mitochondrial iron regulation may provide insights for potential therapeutic targets to improve kidney graft outcomes and other I/R injuries.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Fernando Lucas-Ruiz, Alejandro Penin-Franch, Jose Antonio Pons, Pablo Ramirez, Pablo Pelegrin, Santiago Cuevas, Alberto Baroja-Mazo
Summary: The NLRP3 inflammasome and pyroptosis play important roles in liver transplantation, affecting the progression of liver disease and treatment outcomes. Studying this pathway may lead to new strategies for the future treatment of LT.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Aadil Ali, Aizhou Wang, Rafaela V. P. Ribeiro, Erika L. Beroncal, Cristina Baciu, Marcos Galasso, Bruno Gomes, Andrea Mariscal, Olivia Hough, Edson Brambate, Etienne Abdelnour-Berchtold, Vinicius Michaelsen, Yu Zhang, Anajara Gazzalle, Eddy Fan, Laurent Brochard, Jonathan Yeung, Tom Waddell, Mingyao Liu, Ana C. Andreazza, Shaf Keshavjee, Marcelo Cypel
Summary: Cold static preservation at 10 degrees Celsius can lead to better preservation of donor lungs with improved mitochondrial health and metabolic protection. This approach has been successfully applied in clinical settings, allowing for extended preservation time and improved outcomes for lung transplant recipients. Preserving lungs at 10 degrees Celsius may become the new standard of care for prolonged pulmonary preservation.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Endocrinology & Metabolism
Yingchun Wang, Yun-Yan Xiang, Junichi Sugihara, Wei-Yang Lu, Xiao-Hui Liao, Peter Arvan, Samuel Refetoff, Mingyao Liu
Summary: XB130 critically regulates thyrocyte polarization by functioning as a link between the actin filament cortex and MT network at the apical membrane of thyrocytes. Defects of adaptor scaffold proteins may affect cellular polarity and cytoskeletal structure and function and result in disorders of epithelial function, such as congenital hypothyroidism.
Article
Endocrinology & Metabolism
Hae-Ra Cho, Junichi Sugihara, Hiroki Shimizu, Yun-Yan Xiang, Xiaohui Bai, Yingchun Wang, Xiao-Hui Liao, Sylvia L. Asa, Samuel Refetoff, Mingyao Liu
Summary: The study found that elderly Xb130-deficient mice exhibited severe multinodular goiter (MNG) in their thyroid glands, showing similar pathological features to human MNG. XB130 deficiency significantly exacerbated moderate MNG in elderly mice and reduced the affinity of thyroperoxidase for hydrogen peroxide, suggesting a potential role of oxidative stress in MNG development.
Review
Cardiac & Cardiovascular Systems
Megan Capuzzimati, Olivia Hough, Mingyao Liu
Summary: This article discusses the relationship between cell death and inflammation caused by ischemia-reperfusion in lung transplantation. Different types of cell death and their related molecules are explored. The inhibition of cell death has been explored as a therapeutic approach for ischemia-reperfusion injury in lung transplantation. Understanding these mechanisms is important for donor management, organ preservation, and prevention and treatment of primary graft dysfunction during and after transplantation.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Cardiac & Cardiovascular Systems
Sajad Moshkelgosha, Allen Duong, Gavin Wilson, Tallulah Andrews, Gregory Berra, Benjamin Renaud-Picard, Mingyao Liu, Shaf Keshavjee, Sonya MacParland, Jonathan Yeung, Tereza Martinu, Stephen Juvet
Summary: Single-cell RNA sequencing was used to analyze cells from lung transplant recipients. Two unique subsets of alveolar macrophages were identified in patients with immune-mediated acute lung allograft dysfunction (ALAD). These subsets may be associated with allograft dysfunction and could serve as important therapeutic targets.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Editorial Material
Cardiac & Cardiovascular Systems
Jamie E. Jeon, Mingyao Liu
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2022)
Article
Respiratory System
Cristina Baciu, Jason Shin, Michael Hsin, Marcelo Cypel, Shaf Keshavjee, Mingyao Liu
Summary: This study aims to investigate the metabolomic and transcriptomic profiles in human lungs before and after reperfusion during lung transplantation. The results showed activation of energy metabolism and reduced antioxidative biochemicals during reperfusion. Upregulation of genes related to cytokines and inflammatory mediators were identified. Purine metabolism was found to be the most significantly enriched pathway during reperfusion. Levels of inosine and uric acid were significantly associated with intensive care unit length of stay and ventilation time, indicating the potential role of oxidative stress through purine metabolism pathway in ischaemia reperfusion injury of lung grafts.
Article
Cardiac & Cardiovascular Systems
John Kenneth Peel, Shaf Keshavjee, David Naimark, Mingyao Liu, Lorenzo Del Sorbo, Marcelo Cypel, Kali Barrett, Eleanor M. Pullenayegum, Beate Sander
Summary: This study compared the institutional costs of lung transplantation before and after the availability of EVLP and determined the health-economic impact of EVLP. The study found that EVLP availability was associated with faster progression to transplantation without significant marginal cost increase.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Article
Cardiac & Cardiovascular Systems
Rayoun Ramendra, Andrew T. Sage, Jonathan Yeung, Juan C. Fernandez-Castillo, Marcelo Cuesta, Meghan Aversa, Mingyao Liu, Marcelo Cypel, Shaf Keshavjee, Tereza Martinu
Summary: This study investigates the utility of measuring total bile acids (TBA) in donor large airway bronchial wash (LABW) to predict the performance of donor lungs and recipient outcomes.
JOURNAL OF HEART AND LUNG TRANSPLANTATION
(2023)
Letter
Surgery
Andrea Mariscal, Jussi Tikkanen, Lindsay Calderone, Olivia Hough, Manyin Chen, Tereza Martinu, Stephen Juvet, Marcelo Cypel, Mingyao Liu, Shaf Keshavjee
AMERICAN JOURNAL OF TRANSPLANTATION
(2023)
Review
Pharmacology & Pharmacy
Leeann Yao, Dejan Bojic, Mingyao Liu
Summary: The use of gold nanoparticles in medicine has vast clinical implications and exciting therapeutic potential. Current studies suggest that there are no major safety concerns with the use of gold nanoparticles, but more research and clinical trials are needed to further understand their safety and efficacy in clinical settings.
JOURNAL OF PHARMACEUTICAL ANALYSIS
(2023)
Review
Biotechnology & Applied Microbiology
Antti I. Nykanen, Mingyao Liu, Shaf Keshavjee
Summary: Lung transplantation is often the only option for end-stage lung disease patients. Mesenchymal stromal cells (MSC) have anti-inflammatory and protective effects, which have potential benefits in solid organ transplantation. This review discusses the experimental studies on using MSC to protect donor lungs from ischemia-reperfusion injury and alloimmune responses, as well as the studies on using MSC to prevent or treat chronic lung allograft dysfunction. The ex vivo lung perfusion (EVLP) is also mentioned as an optimal platform for MSC delivery, and the potential of genetic engineering to enhance the therapeutic potential of MSCs.
BIOENGINEERING-BASEL
(2023)
Article
Engineering, Biomedical
Yujian Liu, Kaifu Zheng, Zijie Meng, Lei Wang, Xi Liu, Baolin Guo, Jiankang He, Xiyang Tang, Mingyao Liu, Nan Ma, Xiaofei Li, Jinbo Zhao
Summary: In this study, a cell-free tissue-engineered tracheal substitute was developed using a 3D-printed polycaprolactone scaffold coated with a gelatin-methacryloyl hydrogel. Transforming growth factor-β1 (TGF-β) and stromal cell-derived factor-1α (SDF-1) were embedded in the scaffold to facilitate cell recruitment and differentiation. The tracheal substitute showed positive results in promoting the recruitment of cells and enhancing differentiation towards a chondrocyte phenotype.
Article
Biochemistry & Molecular Biology
Lei Huang, Ravi N. Vellanki, Zhiyuan Zhu, Bradly G. Wouters, Shaf Keshavjee, Mingyao Liu
Summary: Ex vivo lung perfusion (EVLP) has improved lung transplant success by evaluating marginal lungs before transplantation. To develop EVLP as a platform for donor lung reconditioning, a prolonged EVLP and new perfusates providing sufficient nutritional support are necessary. A combination of DMEM and a current EVLP perfusate (Steen solution) enhanced cell function and reduced apoptosis. A new EVLP perfusate, D05D7A solution, based on DMEM was designed and tested, showing improved cell function and higher levels of GSH and HSP70 compared to Steen solution. DMEM-based nutrient-rich perfusate could prolong EVLP and improve donor lung quality for transplantation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Jamie E. Jeon, Lei Huang, Zhiyuan Zhu, Aaron Wong, Shaf Keshavjee, Mingyao Liu
Summary: This study investigated the effects of ischemia-reperfusion and ex vivo lung perfusion (EVLP) on gene expression in human pulmonary microvascular endothelial cells and epithelial cells. The results showed that both cell types exhibited changes in gene expressions after ischemia-reperfusion or EVLP, with the former showing upregulated pro-inflammatory genes and downregulated cell metabolism pathways, while the latter showed downregulation of cell metabolism without any inflammatory signals.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Cell Biology
Yajin Zhao, Kimberly Main, Tanroop Aujla, Shaf Keshavjee, Mingyao Liu
Summary: Organ transplantation is the only treatment option for end-stage organ dysfunction, but it faces various limitations. This study reveals the mechanisms of necroptosis in organ transplantation and identifies potential targeted drugs.