Ex vivo normothermic perfusion in heart transplantation: a review of the TransMedics® Organ Care System

2021 ◽  
Author(s):  
Rebecca Pinnelas ◽  
Jon A Kobashigawa
Keyword(s):  
Viral Vector ◽  
Ex Vivo ◽  
Donation After Cardiac Death ◽  
Machine Perfusion ◽  
Donor Pool ◽  
Complex Anatomy ◽  
Normothermic Perfusion ◽  
End Stage Heart Failure ◽  
End Stage ◽  
Care System

Cardiac transplantation is the gold standard for treatment for select patients with end-stage heart failure, yet donor supply is limited. Ex vivo machine perfusion is an emerging technology capable of safely preserving organs and expanding the viable donor pool. The TransMedics® Organ Care System™ is an investigational device which mimics physiologic conditions while maintaining the heart in a warm, beating state rather than cold storage. The use of Organ Care System allows increased opportunities for using organs from marginal donors, distant procurement sites, donation after cardiac death, and in recipients with complex anatomy. In the future, bioengineering technologies including use of mesenchymal stem cells, viral vector delivery of gene therapy, and alternate devices may further broaden the field of ex vivo machine perfusion.

scholarly journals Zebrafish as a New Tool in Heart Preservation Research

2021 ◽  
Vol 8 (4) ◽  
pp. 39
Author(s):  
Luciana Da Silveira Cavalcante ◽  
Shannon N. Tessier
Keyword(s):  
New Technologies ◽  
Ex Vivo ◽  
Machine Perfusion ◽  
Life Saving ◽  
First Choice ◽  
Heart Preservation ◽  
End Stage Heart Failure ◽  
Ischemia Tolerance ◽  
The 1960S ◽  
End Stage

Heart transplantation became a reality at the end of the 1960s as a life-saving option for patients with end-stage heart failure. Static cold storage (SCS) at 4–6 °C has remained the standard for heart preservation for decades. However, SCS only allows for short-term storage that precludes optimal matching programs, requires emergency surgeries, and results in the unnecessary discard of organs. Among the alternatives seeking to extend ex vivo lifespan and mitigate the shortage of organs are sub-zero or machine perfusion modalities. Sub-zero approaches aim to prolong cold ischemia tolerance by deepening metabolic stasis, while machine perfusion aims to support metabolism through the continuous delivery of oxygen and nutrients. Each of these approaches hold promise; however, complex barriers must be overcome before their potential can be fully realized. We suggest that one barrier facing all experimental efforts to extend ex vivo lifespan are limited research tools. Mammalian models are usually the first choice due to translational aspects, yet experimentation can be restricted by expertise, time, and resources. Instead, there are instances when smaller vertebrate models, like the zebrafish, could fill critical experimental gaps in the field. Taken together, this review provides a summary of the current gold standard for heart preservation as well as new technologies in ex vivo lifespan extension. Furthermore, we describe how existing tools in zebrafish research, including isolated organ, cell specific and functional assays, as well as molecular tools, could complement and elevate heart preservation research.

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.

scholarly journals Ex vivo machine perfusion: current applications and future directions in liver transplantation

2020 ◽  
Author(s):  
Julian Michelotto ◽  
Joseph M. G. V. Gassner ◽  
Simon Moosburner ◽  
Vanessa Muth ◽  
Madhukar S. Patel ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Ex Vivo ◽  
Machine Perfusion ◽  
Donor Organ ◽  
Donor Pool ◽  
Future Directions ◽  
Link Type ◽  
Expanded Criteria ◽  
End Stage ◽  
Liver Machine Perfusion

Abstract Background Liver transplantation is the only curative treatment option for end-stage liver disease; however, its use remains limited due to a shortage of suitable organs. In recent years, ex vivo liver machine perfusion has been introduced to liver transplantation, as a means to expand the donor organ pool. Purpose To present a systematic review of prospective clinical studies on ex vivo liver machine perfusion, in order to assess current applications and highlight future directions. Methods A systematic literature search of both PubMed and ISI web of science databases as well as the ClinicalTrials.gov registry was performed. Results Twenty-one articles on prospective clinical trials on ex vivo liver machine perfusion were identified. Out of these, eight reported on hypothermic, eleven on normothermic, and two on sequential perfusion. These trials have demonstrated the safety and feasibility of ex vivo liver machine perfusion in both standard and expanded criteria donors. Currently, there are twelve studies enrolled in the clinicaltrials.gov registry, and these focus on use of ex vivo perfusion in extended criteria donors and declined organs. Conclusion Ex vivo liver machine perfusion seems to be a suitable strategy to expand the donor pool for liver transplantation and holds promise as a platform for reconditioning diseased organs.

Rewarming Machine Perfusion System for Liver Transplantation

2013 ◽  
Vol 7 (4) ◽  
Author(s):  
Hiromichi Obara ◽  
Naoto Matsuno ◽  
Takanobu Shigeta ◽  
Shin Enosawa ◽  
Toshihiko Hirano ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Organ Donor ◽  
Liver Graft ◽  
Donation After Cardiac Death ◽  
Organ Shortage ◽  
Machine Perfusion ◽  
Porcine Liver ◽  
Donor Pool ◽  
Liver Preservation ◽  
End Stage

The liver is one of the most essential organs, and transplantation is an established treatment for patients with end-stage disease who have lost their liver function. However, organ shortage is a critical problem in transplantation; thus, the development of an innovative preservation system to adopt critical grafts obtained from extended criteria donors or donation after cardiac death donors as viable organs for transplantation is necessary. We recently developed a novel rewarming machine perfusion preservation system for liver transplantation, and herein discuss this system, which allows the perfusion temperature to be controlled during the transition from hypothermic to subnormothermic conditions. This system has two functions: (1) the preservation and recovery of organ function and (2) screening the organ for viability. To achieve these functions, this system has three features: (1) temperature control of the preservation perfusate and liver graft, (2) dual-controlled perfusion of the portal vein and hepatic artery, and (3) real-time monitoring of the perfusion conditions, including the flow rate, perfusion pressure and temperature. This system was useful for liver preservation and for evaluating the graft viability and recovery of functions during machine perfusion before transplantation. This novel rewarming machine preservation system was tested in an experimental model using porcine liver grafts. We report that this system has certain advantages in liver preservation, and believe that this system will positively contribute to the expansion of the organ donor pool.

Ex vivo lung perfusion for donor lung assessment and repair: a review of translational interspecies models

2020 ◽  
Vol 319 (6) ◽  
pp. L932-L940
Author(s):  
Aizhou Wang ◽  
Aadil Ali ◽  
Shaf Keshavjee ◽  
Mingyao Liu ◽  
Marcelo Cypel
Keyword(s):  
Therapeutic Potential ◽  
Ex Vivo ◽  
Small Animal ◽  
Lung Perfusion ◽  
Contributing Factors ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Advantages And Disadvantages ◽  
Number Of Patients ◽  
End Stage

For patients with end-stage lung disease, lung transplantation is a lifesaving therapy. Currently however, the number of patients who require a transplant exceeds the number of donor lungs available. One of the contributing factors to this is the conservative mindset of physicians who are concerned about transplanting marginal lungs due to the potential risk of primary graft dysfunction. Ex vivo lung perfusion (EVLP) technology has allowed for the expansion of donor pool of organs by enabling assessment and reconditioning of these marginal grafts before transplant. Ongoing efforts to optimize the therapeutic potential of EVLP are underway. Researchers have adopted the use of different large and small animal models to generate translational preclinical data. This includes the use of rejected human lungs, pig lungs, and rat lungs. In this review, we summarize some of the key current literature studies relevant to each of the major EVLP model platforms and identify the advantages and disadvantages of each platform. The review aims to guide investigators in choosing an appropriate species model to suit their specific goals of study, and ultimately aid in translation of therapy to meet the growing needs of the patient population.

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.

Ex Vivo Lung Perfusion: A Review of Research and Clinical Practices

2020 ◽  
Vol 24 (1) ◽  
pp. 34-44 ◽  
Author(s):  
Patrick G. Chan ◽  
Akshay Kumar ◽  
Kathirvel Subramaniam ◽  
Pablo G. Sanchez
Keyword(s):  
Lung Disease ◽  
Ex Vivo ◽  
Conventional Technique ◽  
Lung Perfusion ◽  
Clinical Practices ◽  
Donor Pool ◽  
Ex Vivo Lung Perfusion ◽  
Number Of Patients ◽  
End Stage ◽  
Potential Tool

End-stage lung disease is ultimately treated with lung transplantation. However, there is a paucity of organs with an increasing number of patients being diagnosed with end-stage lung disease. Ex vivo lung perfusion has emerged as a potential tool to assess the quality and to recondition marginal donor lungs prior to transplantation with the goal of increasing the donor pool. This technology has shown promise with similar results compared with the conventional technique of cold static preservation in terms of primary graft dysfunction and overall outcomes. This review provides an update on the results and uses of this technology. The review will also summarize clinical studies and techniques in reconditioning and assessing lungs on ex vivo lung perfusion. Last, we discuss how this technology can be applied to fields outside of transplantation such as thoracic oncology and bioengineering.

scholarly journals Development of ex vivo normothermic perfusion as an innovative method to assess pancreases after preservation

2021 ◽  
Vol 2 (4) ◽  
Author(s):  
Ann Ogbemudia
Keyword(s):  
Cold Storage ◽  
Ex Vivo ◽  
Gas Analysis ◽  
Machine Perfusion ◽  
Assessment Strategy ◽  
Hypothermic Machine Perfusion ◽  
Normothermic Perfusion ◽  
Pancreas Preservation ◽  
Normothermic Machine Perfusion ◽  
Lactate Levels

Ann Ogbemudia, Julien Branchereau (Joint first authors), Gabriella Hakim, Fungai Dengu, FaysalEl-Gilani, John Mulvey, Kaithlyn Rozenberg, Thomas Prudhomme, Letizia Lo Faro, James Hunter,Paul Johnson, Rutger Ploeg and Peter Friend   Objective Static cold storage (SCS) is the standard method for pancreas preservation but does not facilitate objective organ assessment prior to transplantation. Normothermic machine perfusion (NMP) has been used to test other abdominal and thoracic organs’ function and viability in transplantation settings. Our aim was to develop a NMP protocol specific for pancreases and then investigate its potential as an organ assessment strategy. Method 8 porcine pancreases were procured in conditions replicating donation after circulatory death with warm ischaemia time of 25 minutes. After 3 hours of static cold storage (SCS) the pancreases were divided into 3 experimental groups 1) the feasibility group (n=2) that underwent 2.5 hours of NMP 2) the SCS group (n = 2) that underwent an additional 6 hours of SCS prior to assessment on NMP for an hour and 3) the Oxygenated Hypothermic Machine Perfusion (oxyHMP) group (n = 4) that underwent 6 hours of oxyHMP followed by 1-hour assessment on NMP. The NMP protocol used autologous, leucodepleted blood delivered at a mean arterial pressure of 40mmHg with a temperature of 37oC. At timed intervals during NMP, perfusate samples were collected for gas analysis and perfusion parameters were recorded. Results The feasibility group was used to develop the NMP protocol and demonstrated stable perfusion parameters throughout NMP. Compared to the SCS group the oxyHMP group demonstrated better average perfusion characteristics with lower resistances, higher flow rates, lower mean lactate levels and physiological pH. The oxyHMP group maintained normal macroscopic appearances during NMP. At the end of NMP the SCS group had an average 32% weight increase compared to the oxyHMP group that were found to have a 17% weight reduction. Conclusion Normothermic machine perfusion of whole pancreases is feasible after cold preservation and potentially useful as an assessment strategy. Furthermore, it demonstrated that oxygenated HMP may be beneficial for pancreas preservation compared to SCS.

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