scholarly journals Transcriptomic profiles of human livers undergoing rewarming machine perfusion before transplantation—first insights

2021 ◽  
Author(s):  
Dieter Paul Hoyer ◽  
Sandra Swoboda ◽  
Juergen Walter Treckmann ◽  
Tamas Benkö ◽  
Andreas Paul ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Human Liver ◽  
Molecular Mechanisms ◽  
Machine Perfusion ◽  
Gene Expressions ◽  
Human Liver Tissue ◽  
Transcriptional Changes ◽  
Human Livers ◽  
Next Generation Sequencing Ngs ◽  
Upregulated Genes

AbstractMachine perfusion by controlled oxygenated rewarming (COR) is feasible and safe in clinical application and result in a promising outcome. This study utilizes next-generation sequencing (NGS) to investigate the transcriptome of human liver tissue undergoing COR before liver transplantation. Cold-stored livers were subjected to machine-assisted slow COR for ~120 min before transplantation. Biopsies were taken before (preCOR) and after COR (postCOR) and 1 h after reperfusion (postRep). The samples were sequenced, using RNA-seq to analyze differential transcriptional changes between the different stages and treatments of the grafts. Comparison of differential gene expression preCOR and postCOR demonstrated 10 upregulated genes. postRep 97 and 178 genes were upregulated and 7 and 13 downregulated compared to preCOR and postCOR, respectively. A shift of gene expressions by machine perfusion to the TGF-beta pathway was observed. The present study demonstrates distinct transcriptome profiles associated with machine perfusion by COR and transplantation of human livers. Such data provide a deeper understanding of the molecular mechanisms of machine perfusion technology in human liver transplantation.

scholarly journals Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials

2020 ◽  
Vol 40 (03) ◽  
pp. 264-281 ◽  
Author(s):  
E. Bonaccorsi-Riani ◽  
I.M.A. Brüggenwirth ◽  
J.E. Buchwald ◽  
S. Iesari ◽  
P.N. Martins
Keyword(s):  
Liver Transplantation ◽  
Clinical Trials ◽  
Ex Situ ◽  
Machine Perfusion ◽  
Correct Trial ◽  
Gold Standard Method ◽  
Liver Preservation ◽  
Mature Phase ◽  
Normothermic Machine Perfusion ◽  
Human Livers

AbstractMachine perfusion (MP) preservation is potentially one of the most significant improvements in the field of liver transplantation in the last 20 years, and it has been considered a promising strategy for improved preservation and ex situ evaluation of extended criteria donor (ECD) organs. However, MP preservation adds significant cost and logistical considerations to liver transplantation. MP protocols are mainly classified according to the perfusion temperature with hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) being the two categories most studied so far. After extensive preclinical work, MP entered the clinical setting, and there are now several studies that demonstrated feasibility and safety. However, because of the limited quality of clinical trials, there is no compelling evidence of superiority in preservation quality, and liver MP is still considered experimental in most countries. MP preservation is moving to a more mature phase, where ongoing and future studies will bring new evidence in order to confirm their superiority in terms of clinical outcomes, organ utilization, and cost-effectiveness. Here, we present an overview of all preclinical MP studies using discarded human livers and liver MP clinical trials, and discuss their results. We describe the different perfusion protocols, pitfalls in MP study design, and provide future perspectives. Recent trials in liver MP have revealed unique challenges beyond those seen in most clinical studies. Randomized trials, correct trial design, and interpretation of data are essential to generate the data necessary to prove if MP will be the new gold standard method of liver preservation.

scholarly journals First human liver transplantation using a marginal allograft resuscitated by normothermic machine perfusion

2015 ◽  
Vol 22 (1) ◽  
pp. 120-124 ◽  
Author(s):  
Thamara Perera ◽  
Hynek Mergental ◽  
Barney Stephenson ◽  
Garrett R. Roll ◽  
Hentie Cilliers ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Human Liver ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals A novel model for ex situ reperfusion of the human liver following subnormothermic machine perfusion

TECHNOLOGY ◽  
2017 ◽  
Vol 05 (04) ◽  
pp. 196-200 ◽  
Author(s):  
James H. Avruch ◽  
Bote G. Bruinsma ◽  
Pepijn D. Weeder ◽  
Gautham V. Sridharan ◽  
Robert J. Porte ◽  
...  
Keyword(s):  
Human Liver ◽  
Ex Situ ◽  
Machine Perfusion ◽  
Human Donor ◽  
Liver Preservation ◽  
Atp Levels ◽  
Preservation Method ◽  
Human Livers ◽  
Novel Model ◽  
Bile Production

Machine perfusion-based organ preservation techniques are prudently transitioning into clinical practice. Although experimental data is compelling, the outcomes in the highly variable clinical donation-transplantation setting are unpredictable. Here, we offer an intermediate tool for pre-clinical assessment of human donor livers. We present a model for ex situ reperfusion of discarded human livers and report on its application in three human livers that have undergone subnormothermic (21[Formula: see text]C) machine perfusion as an experimental preservation method. During reperfusion, the livers macroscopically reperfused in the first 15 minutes, and remained visually well-perfused for 3 hours of ex situ reperfusion. Bile production and oxygen consumption were observed throughout ex situ reperfusion. ATP levels increased 4.25-fold during SNMP. Between the end of SNMP and the end of reperfusion ATP levels dropped 45%. ALT levels in blood increased rapidly in the first 30 minutes and ALT release continued to taper off towards the end of perfusion. Release of CRP, TNF-[Formula: see text], IL-1[Formula: see text], and IL-12, IFN-[Formula: see text] was sustained during reperfusion. These findings support the use of this model for the evaluation of novel human liver preservation techniques.

scholarly journals Cellular and molecular mechanisms of abnormal calcification following ischemia–reperfusion injury in human liver transplantation

2007 ◽  
Vol 20 (3) ◽  
pp. 357-366 ◽  
Author(s):  
Fariba Kalantari ◽  
Dengshun Miao ◽  
Anouk Emadali ◽  
George N Tzimas ◽  
David Goltzman ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Reperfusion Injury ◽  
Human Liver ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion

scholarly journals Transcriptomics Analysis of Primordium Formation in Pleurotus eryngii

Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 1863
Author(s):  
Dou Ye ◽  
Fang Du ◽  
Yajie Zou ◽  
Qingxiu Hu
Keyword(s):  
Differentially Expressed Genes ◽  
Molecular Mechanisms ◽  
Pleurotus Eryngii ◽  
Differentially Expressed ◽  
Light Perception ◽  
Cell Wall Degradation ◽  
Molecular Processes ◽  
Carbohydrate Hydrolysis ◽  
Transcriptional Changes ◽  
Upregulated Genes

Primordium formation is an important stage preceding the growth and development of the Pleurotus eryngii fruiting body. However, the molecular mechanisms underlying primordium formation remain unclear. In the present study, comparative transcriptomics was performed between mature mycelia and primordium to analyze the transcriptional properties during primordium formation in P. eryngii. A total of 19,655 differentially expressed genes (10,718 upregulated genes and 8937 downregulated genes) were identified. These differentially expressed genes were involved in cell wall degradation, carbohydrate hydrolysis, light perception, and cAMP signal transduction. These results aid further understanding of the transcriptional changes and the molecular processes underlying primordium formation and differentiation, which may lay the foundation for improving the cultivation and quality control of P. eryngii.

Sign in / Sign up

Export Citation Format

Share Document