scholarly journals Successful Transplantation of Human Kidneys Deemed Untransplantable but Resuscitated by Ex Vivo Normothermic Machine Perfusion

2016 ◽  
Vol 16 (11) ◽  
pp. 3282-3285 ◽  
Author(s):  
S. A. Hosgood ◽  
K. Saeb-Parsy ◽  
M. O. Hamed ◽  
M. L. Nicholson
Keyword(s):  
Ex Vivo ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion ◽  
Successful Transplantation

Hyperspectral imaging for ex-vivo organ characterization during normothermic machine perfusion

2018 ◽  
Vol 17 (2) ◽  
pp. e767 ◽  
Author(s):  
W. Markgraf ◽  
M.W.W. Janssen ◽  
J. Lilienthal ◽  
P. Feistel ◽  
C. Thiele ◽  
...  
Keyword(s):  
Hyperspectral Imaging ◽  
Ex Vivo ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals Novel delivery of cellular therapy to reduce ischaemia reperfusion injury in kidney transplantation

2019 ◽  
Author(s):  
Emily R Thompson ◽  
Lucy Bates ◽  
Ibrahim K Ibrahim ◽  
Avinash Sewpaul ◽  
Ben Stenberg ◽  
...  
Keyword(s):  
Cell Therapy ◽  
Reperfusion Injury ◽  
Cellular Therapy ◽  
Ex Vivo ◽  
Left Kidney ◽  
Kidney Injury ◽  
Machine Perfusion ◽  
Ischaemia Reperfusion Injury ◽  
Ischaemia Reperfusion ◽  
Normothermic Machine Perfusion

AbstractEx-vivo normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for direct delivery of cellular therapeutics to optimise organ quality prior to transplantation. Multipotent Adult Progenitor Cells (MAPC®) possess potent immunomodulatory properties which could prove beneficial in minimising subsequent ischaemia reperfusion injury. We investigated the potential reconditioning capability of MAPC cells in kidney NMP.MethodsPairs (5) of human kidneys from the same donor were simultaneously perfused for 7 hours. The right or left kidney was randomly allocated to receive MAPC treatment. Serial samples of perfusate, urine and tissue biopsies were taken for comparison with the control paired kidney.ResultsMAPC-treated kidneys demonstrated improved urine output (p<0.01), decreased expression of the kidney injury biomarker NGAL (p<0.01), improved microvascular perfusion on contrast enhanced ultrasound (cortex p<0.05, medulla p<0.01), downregulation of IL-1β (p<0.05) and upregulation of IL-10 (p<0.05) and Indolamine-2, 3-dioxygenase (p<0.05). A mouse model of intraperitoneal chemotaxis demonstrated decreased neutrophil recruitment when stimulated with perfusate from MAPC-treated kidneys (p<0.01). Immunofluorescence revealed pre-labelled MAPC cells home to the perivascular space in the kidneys during NMP. MAPC therapy was not associated with detrimental physiological or embolic events.ConclusionWe report the first successful delivery of cellular therapy to a kidney during NMP. Kidneys treated with MAPC cells demonstrate improvement in clinically relevant functional parameters and injury biomarkers. This novel method of cell therapy delivery provides an exciting opportunity to recondition organs prior to clinical transplantation.One Sentence SummaryEx-vivo reconditioning of human kidneys using Multipotent Adult Progenitor Cell therapy delivered during normothermic machine perfusion.

scholarly journals Normothermic Machine Perfusion (NMP) of the Liver as a Platform for Therapeutic Interventions during Ex-Vivo Liver Preservation: A Review

2020 ◽  
Vol 9 (4) ◽  
pp. 1046 ◽  
Author(s):  
Fungai Dengu ◽  
Syed Hussain Abbas ◽  
Georg Ebeling ◽  
David Nasralla
Keyword(s):  
Ex Vivo ◽  
Organ Donor ◽  
Therapeutic Interventions ◽  
Machine Perfusion ◽  
Real Potential ◽  
Ischaemia Reperfusion Injury ◽  
Donor Pool ◽  
Liver Preservation ◽  
Ischaemia Reperfusion ◽  
Normothermic Machine Perfusion

Liver transplantation is increasingly dependent on the use of extended criteria donors (ECD) to increase the organ donor pool and address rising demand. This has necessitated the adoption of innovative technologies and strategies to protect these higher-risk grafts from the deleterious effects of traditional preservation and ischaemia reperfusion injury (IRI). The advent of normothermic machine perfusion (NMP) and rapid growth in the clinical adoption of this technology has accelerated efforts to utilise NMP as a platform for therapeutic intervention to optimise donor livers. In this review we will explore the emerging preclinical data related to ameliorating the effects of IRI, protecting the microcirculation and reducing the immunogenicity of donor organs during NMP. Exploiting the window of opportunity afforded by NMP, whereby the liver can be continuously supported and functionally assessed while therapies are directly delivered during the preservation period, has clear logistical and theoretical advantages over current preservation methods. The clinical translation of many of the therapeutic agents and strategies we will describe is becoming more feasible with widespread adaptation of NMP devices and rapid advances in molecular biology and gene therapy, which have substantially improved the performance of these agents. The delivery of novel therapeutics during NMP represents one of the new frontiers in transplantation research and offers real potential for successfully tackling fundamental challenges in transplantation such as IRI.

Normothermic machine perfusion of donor-lungs ex-vivo

2020 ◽  
Vol 25 (3) ◽  
pp. 285-292 ◽  
Author(s):  
Jenny Gilmour ◽  
Chelsea Griffiths ◽  
Tom Pither ◽  
William E. Scott ◽  
Andrew J. Fisher
Keyword(s):  
Ex Vivo ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals O3 Ex vivo normothermic machine perfusion facilitates gymnotic delivery of RNA interference therapeutics in donor kidneys

2021 ◽  
Vol 108 (Supplement_5) ◽  
Author(s):  
E R Thompson ◽  
A Sewpaul ◽  
R Figuereido ◽  
L Bates ◽  
J R Ferdinand ◽  
...  
Keyword(s):  
Rna Interference ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Machine Perfusion ◽  
Endosomal Sorting ◽  
Early Endosomes ◽  
Normothermic Machine Perfusion ◽  
Rnai Therapeutics ◽  
The Many

Abstract Introduction Normothermic machine perfusion (NMP) of donor kidneys prior to transplantation provides a platform for delivery of novel therapeutics to optimize organ quality. This includes RNA interference (RNAi) therapeutics e.g. antisense oligonucleotides (ASO) that block detrimental microRNAs. The intracellular kinetics of RNAi therapeutics are crucial for their pharmacological effect, however, it remains poorly understood. NMP provides an ideal platform to investigate this further. Method During NMP, human kidneys (n = 12) were treated for 6 hours with a fluorescently-labelled ASO designed to block microRNA-24-3p activity. Biopsies were taken at 0, 2, 4, and 6 hours. Kidney sections were stained with antibodies against early endosomes (Rab5), late endosomes (Rab7), RNA-induced silencing complexes (GW182) and lysosomes (LAMP2). Confocal microscopy images were obtained and co-localisation quantified using Hugyens™ software following batch deconvolution. The global transcriptomic impact of ASO therapy was also assessed using RNA sequencing. Result Following 2 hours of NMP, ASO was primarily found in tubular epithelial cells. Co-localisation studies revealed ASO uptake via endocytosis and endosomal sorting occurring during NMP. This was followed by cytoplasmic escape and co-localisation of ASO with GW182 proteins. This pattern of co-localisation was not seen in scrambled sequence or cold perfusion controls. RNAseq analysis revealed a decrease in inflammatory pathways and upregulation of microRNA-24-3p targets. Discussion This is the first study to demonstrate NMP facilitates gymnotic ASO delivery directly into the RISC, whereby, it blocks microRNA-mediated mRNA silencing and increases bioavailability of protective targets. This study highlights the capacity of NMP to re-programme gene expression in donor kidneys using RNAi therapeutics. Take-home Message Ex vivo normothermic machine perfusion of donor kidneys provides a unique window of opportunity prior to transplantation when we can deliver therapies to improve the quality of the organ. Novel genetic therapies designed to protect kidneys against ischemia reperfusion injury could potentially increase organ utilisation and improve post-transplant outcomes for the many patients on the kidney transplant waiting list.

Ex Vivo Normothermic Machine Perfusion Is Safe, Simple, and Reliable

2014 ◽  
Vol 22 (1) ◽  
pp. 61-69 ◽  
Author(s):  
Ahmed Nassar ◽  
Qiang Liu ◽  
Kevin Farias ◽  
Giuseppe D’Amico ◽  
Cynthia Tom ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Machine Perfusion ◽  
Normothermic Machine Perfusion

scholarly journals Criteria for viability assessment of discarded human donor livers during ex-vivo normothermic machine perfusion

2014 ◽  
Vol 31 (4) ◽  
pp. 239
Author(s):  
Michael E. Sutton ◽  
Sanna op den Dries ◽  
Negin Karimian ◽  
Marieke T. de Boer ◽  
Janneke Wiersema-Buist ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Machine Perfusion ◽  
Viability Assessment ◽  
Human Donor ◽  
Normothermic Machine Perfusion

scholarly journals Ex Vivo Mesenchymal Stem Cell Therapy to Regenerate Machine Perfused Organs

2021 ◽  
Vol 22 (10) ◽  
pp. 5233
Author(s):  
Christina Bogensperger ◽  
Julia Hofmann ◽  
Franka Messner ◽  
Thomas Resch ◽  
Andras Meszaros ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Ex Situ ◽  
Machine Perfusion ◽  
Donor Pool ◽  
Mesenchymal Stem Cell Therapy ◽  
Perfusion Process ◽  
Normothermic Machine Perfusion ◽  
Clinical Benefits ◽  
Organ Quality ◽  
End Stage

Transplantation represents the treatment of choice for many end-stage diseases but is limited by the shortage of healthy donor organs. Ex situ normothermic machine perfusion (NMP) has the potential to extend the donor pool by facilitating the use of marginal quality organs such as those from donors after cardiac death (DCD) and extended criteria donors (ECD). NMP provides a platform for organ quality assessment but also offers the opportunity to treat and eventually regenerate organs during the perfusion process prior to transplantation. Due to their anti-inflammatory, immunomodulatory and regenerative capacity, mesenchymal stem cells (MSCs) are considered as an interesting tool in this model system. Only a limited number of studies have reported on the use of MSCs during ex situ machine perfusion so far with a focus on feasibility and safety aspects. At this point, no clinical benefits have been conclusively demonstrated, and studies with controlled transplantation set-ups are urgently warranted to elucidate favorable effects of MSCs in order to improve organs during ex situ machine perfusion.

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