Hyperspectral Imaging and Machine Perfusion in Solid Organ Transplantation: Clinical Potentials of Combining Two Novel Technologies

Organ transplantation survival rates have continued to improve over the last decades, mostly due to reduction of mortality early after transplantation. The advancement of the field is facilitating a liberalization of the access to organ transplantation with more patients with higher risk profile being added to the waiting list. At the same time, the persisting organ shortage fosters strategies to rescue organs of marginal donors. In this regard, hypothermic and normothermic machine perfusion are recognized as one of the most important developments in the modern era. Owing to these developments, novel non-invasive tools for the assessment of organ quality are on the horizon. Hyperspectral imaging represents a potentially suitable method capable of evaluating tissue morphology and organ perfusion prior to transplantation. Considering the changing environment, we here discuss the hypothetical combination of organ machine perfusion and hyperspectral imaging as a prospective feasibility concept in organ transplantation.

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Combination of mesenchymal stromal cells and machine perfusion is a novel strategy for organ preservation in solid organ transplantation

Cell and Tissue Research ◽

10.1007/s00441-020-03406-3 ◽

2021 ◽

Author(s):

Lingfei Zhao ◽

Chenxia Hu ◽

Fei Han ◽

Dajin Chen ◽

Yanhong Ma ◽

...

Keyword(s):

Organ Transplantation ◽

Mesenchymal Stromal Cells ◽

Stromal Cells ◽

Organ Preservation ◽

Ex Vivo ◽

Solid Organ Transplantation ◽

Organ Shortage ◽

Solid Organ ◽

Machine Perfusion ◽

Organ Function

AbstractOrgan preservation is a prerequisite for an urgent increase in the availability of organs for solid organ transplantation (SOT). An increasing amount of expanded criteria donor (ECD) organs are used clinically. Currently, the paradigm of organ preservation is shifting from simple reduction of cellular metabolic activity to maximal simulation of an ex vivo physiological microenvironment. An ideal organ preservation technique should not only preserve isolated organs but also offer the possibility of rehabilitation and evaluation of organ function prior to transplantation. Based on the fact that mesenchymal stromal cells (MSCs) possess strong regeneration properties, the combination of MSCs with machine perfusion (MP) is expected to be superior to conventional preservation methods. In recent years, several studies have attempted to use this strategy for SOT showing promising outcomes. With better organ function during ex vivo preservation and the potential of utilization of organs previously deemed untransplantable, this strategy is meaningful for patients with organ failure to help overcome organ shortage in the field of SOT.

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The Endothelial Glycocalyx and Organ Preservation—From Physiology to Possible Clinical Implications for Solid Organ Transplantation

International Journal of Molecular Sciences ◽

10.3390/ijms22084019 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4019

Author(s):

Simon Mathis ◽

Gabriel Putzer ◽

Stefan Schneeberger ◽

Judith Martini

Keyword(s):

Organ Transplantation ◽

Organ Preservation ◽

Ischemia Reperfusion Injury ◽

Current Knowledge ◽

Ischemia Reperfusion ◽

Solid Organ Transplantation ◽

Endothelial Glycocalyx ◽

Solid Organ ◽

Machine Perfusion ◽

Normothermic Machine Perfusion

The endothelial glycocalyx is a thin layer consisting of proteoglycans, glycoproteins and glycosaminoglycans that lines the luminal side of vascular endothelial cells. It acts as a barrier and contributes to the maintenance of vascular homeostasis and microperfusion. During solid organ transplantation, the endothelial glycocalyx of the graft is damaged as part of Ischemia Reperfusion Injury (IRI), which is associated with impaired organ function. Although several substances are known to mitigate glycocalyx damage, it has not been possible to use these substances during graft storage on ice. Normothermic machine perfusion (NMP) emerges as an alternative technology for organ preservation and allows for organ evaluation, but also offers the possibility to treat and thus improve organ quality during storage. This review highlights the current knowledge on glycocalyx injury during organ transplantation, presents ways to protect the endothelial glycocalyx and discusses potential glycocalyx protection strategies during normothermic machine perfusion.

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Application of Mesenchymal Stem Cells During Machine Perfusion: An Emerging Novel Strategy for Organ Preservation

Frontiers in Immunology ◽

10.3389/fimmu.2021.713920 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jiale Li ◽

Qinbao Peng ◽

Ronghua Yang ◽

Kunsheng Li ◽

Peng Zhu ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Organ Transplantation ◽

Organ Preservation ◽

Ischemia Reperfusion ◽

Solid Organ Transplantation ◽

Therapeutic Effects ◽

Solid Organ ◽

Machine Perfusion ◽

Marginal Grafts

Although solid organ transplantation remains the definitive management for patients with end-stage organ failure, this ultimate treatment has been limited by the number of acceptable donor organs. Therefore, efforts have been made to expand the donor pool by utilizing marginal organs from donation after circulatory death or extended criteria donors. However, marginal organs are susceptible to ischemia-reperfusion injury (IRI) and entail higher requirements for organ preservation. Recently, machine perfusion has emerged as a novel preservation strategy for marginal grafts. This technique continually perfuses the organs to mimic the physiologic condition, allows the evaluation of pretransplant graft function, and more excitingly facilitates organ reconditioning during perfusion with pharmacological, gene, and stem cell therapy. As mesenchymal stem cells (MSCs) have anti-oxidative, immunomodulatory, and regenerative properties, mounting studies have demonstrated the therapeutic effects of MSCs on organ IRI and solid organ transplantation. Therefore, MSCs are promising candidates for organ reconditioning during machine perfusion. This review provides an overview of the application of MSCs combined with machine perfusion for lung, kidney, liver, and heart preservation and reconditioning. Promising preclinical results highlight the potential clinical translation of this innovative strategy to improve the quality of marginal grafts.

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Recent options in drug therapy after solid organ transplantation

Orvosi Hetilap ◽

10.1556/oh.2012.29343 ◽

2012 ◽

Vol 153 (33) ◽

pp. 1294-1301

Author(s):

Balázs Pőcze ◽

Péter Németh ◽

Róbert Langer

Keyword(s):

Immune Response ◽

Organ Transplantation ◽

Survival Rates ◽

Solid Organ Transplantation ◽

Tolerance Induction ◽

Calcineurin Inhibitors ◽

Immunosuppressive Drugs ◽

Solid Organ ◽

Patient And Graft Survival

Solid organ transplantation has shown improvement in patient and graft survival rates due to the development of immunosuppression in the last fifty years; however only the last two decades led to the development of new, baseline immunosuppressive drugs that avoid the unlikely side effects of calcineurin inhibitors, especially nephrotoxicity. The transplanted organ is foreign to the host and, therefore, it induces a complex immune response of the recipient. In this review, a brief outline of immune response is given, followed by the introduction of new immunosuppressive drugs acting via variant pathways. These are compounds which are already in use or becoming shortly available and are potential future alternatives for the calcineurin inhibitors. This paper highlights the role of co-stimulation blockade with belatacept and the recently even more intensively studied field of tolerance induction. Orv. Hetil., 2012, 153, 1294–1301.

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Machine perfusion in solid organ transplantation: where is the benefit?

Langenbeck s Archives of Surgery ◽

10.1007/s00423-014-1161-2 ◽

2014 ◽

Vol 399 (4) ◽

pp. 421-427 ◽

Cited By ~ 2

Author(s):

Helge Bruns ◽

Peter Schemmer

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Solid Organ ◽

Machine Perfusion

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Impact of Melatonin in Solid Organ Transplantation—Is It Time for Clinical Trials? A Comprehensive Review

International Journal of Molecular Sciences ◽

10.3390/ijms19113509 ◽

2018 ◽

Vol 19 (11) ◽

pp. 3509 ◽

Cited By ~ 2

Author(s):

Philipp Stiegler ◽

Augustinas Bausys ◽

Bettina Leber ◽

Kestutis Strupas ◽

Peter Schemmer

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Experimental Studies ◽

Organ Shortage ◽

Solid Organ ◽

Comprehensive Overview ◽

Donor Pool ◽

End Stage ◽

New Strategies ◽

Significant Mortality

Solid organ transplantation is the “gold standard” for patients with end-stage organ disease. However, the supply of donor organs is critical, with an increased organ shortage over the last few years resulting in a significant mortality of patients on waiting lists. New strategies to overcome the shortage of organs are urgently needed. Some experimental studies focus on melatonin to improve the donor pool and to protect the graft; however, current research has not reached the clinical level. Therefore, this review provides a comprehensive overview of the data available, indicating that clinical evaluation is warranted.

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Szervkonzerválás gépi perfúzióval: új lehetőségek a hasi szervek transzplantációjában

Orvosi Hetilap ◽

10.1556/650.2018.31282 ◽

2018 ◽

Vol 159 (46) ◽

pp. 1882-1890 ◽

Cited By ~ 1

Author(s):

Dániel Wettstein ◽

Mátyás Hamar ◽

Orsolya Cseprekál ◽

Szabolcs József Tóth ◽

Balázs Rózsa ◽

...

Keyword(s):

New Technology ◽

Solid Organ Transplantation ◽

Clinical Results ◽

Organ Shortage ◽

Solid Organ ◽

Machine Perfusion ◽

Promising Tool ◽

Marginal Grafts ◽

Short And Long Term ◽

And Function

Abstract: Machine perfusion of marginal grafts might be a possible solution to organ shortage and a promising tool for reducing waiting list morbidity and mortality. In recent years, optimizing the circumstances of organ preservation prior to implantation via machine perfusion has become a hot topic of research. Machine perfusion offers a platform for organ reconditioning, assessment of cell viability and function, pharmacological preconditioning, prolongation of preservation time (ischemia time) and finally reducing graft injury. The objective of the new technology is to increase the pool of transplantable organs safely. Multicentric prospective studies have been evaluating the short and long term outcomes of different methods, however, several questions still remain unanswered. This review summarizes the recent advances in the field of machine perfusion, focusing on preclinical and clinical results. Machine perfusion seems to be a new milestone in the modern era of solid organ transplantation. Orv Hetil. 2018; 159(46): 1882–1890.

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Remaining Physiological Barriers in Porcine Kidney Xenotransplantation: Potential Pathways behind Proteinuria as well as Factors Related to Growth Discrepancies following Pig-to-Kidney Xenotransplantation

Journal of Immunology Research ◽

10.1155/2018/6413012 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 5

Author(s):

Jigesh A. Shah ◽

Miguel A. Lanaspa ◽

Tatsu Tanabe ◽

Hironosuke Watanabe ◽

Richard J. Johnson ◽

...

Keyword(s):

Organ Transplantation ◽

Solid Organ Transplantation ◽

Large Animal ◽

Organ Shortage ◽

Solid Organ ◽

Porcine Kidney ◽

Barriers To Success ◽

Large Animal Models ◽

Number Of Patients ◽

Causative Factors

Considerable shortages in the supply of available organs continue to plague the field of solid organ transplantation. Despite changes in allocation, as well as the utilization of extended criteria and living donors, the number of patients waiting for organs continues to grow at an alarming pace. Xenotransplantation, cross-species solid organ transplantation, offers one potential solution to this dilemma. Previous extensive research dedicated to this field has allowed for resolution of xenograft failure due to acute rejection, leaving new areas of unresolved challenges as barriers to success in large animal models. Specific to kidney xenotransplantation, recent data seems to indicate that graft compromise can occur due to discrepancies in growth between breeds of donors and significant proteinuria leading to nephrotic syndrome in the recipient. Given these potential limitations, herein, we review potential pathways behind proteinuria, as well as potential causative factors related to growth discrepancies. Control of both of these has the potential to allow xenotransplantation to become clinically applicable in an effort to resolve this organ shortage crisis.

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