Methods Of Organ Preservation Research Articles

Laryngeal cancer relative survival trends from 1972 to 2021 in the Nordic countries.

Changes in treatment approaches, characterised by the shift from laryngectomy to a focus on organ-preserving methods may have potentially resulted in lower survival. We aim to identify differences in survival trends for laryngeal cancer (LC) in the Nordic countries over a period of 50 years, and discuss the potential impact of factors such as changes in treatment protocols. Five-year relative survival (RS) data from 1972 to 2021 were obtained from the NORDCAN database 2.0 which included 33,692 LC cases, of which 85% were diagnosed among men. In the NORDCAN database, the age-standardised RS is calculated using the Pohar Perme estimator with individual International Cancer Survival Standards weights. Joinpoint regression models were used to assess potential shifts in trend over the years in RS. While Denmark and Norway demonstrated an increasing trend in 5-year RS from 1972 to 2021, in Finland and Sweden, the 5-year RS among men remained static, without any discernible significant trend. Over the 30-year period from 1992-1996 to 2017-2021, RS improved by 9, 4, 13, and 2 percentage points in Denmark, Finland, Norway, and Sweden, respectively. Among women in Sweden, a linear negative trend was observed, noticeable as a 16 percentage-point decline in 5-year RS from the earliest to the latest period. The underlying causes for the differences in survival trends remain unclear. Besides differences in treatment protocols, several other factors can affect RS making the interpretation of RS trends challenging.

Recent solid-phase microextraction-based analytical approaches for the profiling of biliary bile acids in pre-transplant assessments of liver grafts subjected to normothermic ex vivo liver perfusion

BackgroundLiver transplantation is the definitive treatment for end-stage liver failure, but the scarcity of donor organs remains a significant challenge. Leveraging organs from extended criteria donors (ECD) offers a potential avenue to address worldwide shortages, though these organs are more susceptible to post-reperfusion injury. This study explores the use of normothermic ex vivo liver perfusion (NEVLP) as a method for organ preservation – an approach that sustains liver metabolism and facilitates pre-transplant assessments of organ viability via bile analysis. The focal point of this study revolves on the development of analytical methods for determining the bile acid profile throughout the peritransplantation period as a potential indicator of liver function and viability. ResultsThe study optimized and validated a high-throughput analytical method to quantify selected bile acids in bile samples using a thin-film microextraction-liquid chromatography-mass spectrometry (TFME-LC-MS) platform. Furthermore, it introduced a solid-phase microextraction-microfluidic open interface-mass spectrometry (SPME-MOI-MS) method for rapid direct analysis of bile acid isobar groups. In the animal study, discernible variations in the concentrations of specific bile acids were observed between donors after circulatory death (DCD) and heart-beating donors (HBD), particularly following normothermic perfusion and reperfusion. Noteworthy fluctuations in individual bile acid concentrations were observed throughout the entire organ transplantation process, with taurocholic acid (TCA), glycocholic acid (GCA), and glycochenodeoxycholic acid (GCDCA) emerging as promising indicators of organ quality. The efficacy of the SPME-MOI-MS platform in corroborating these trends highlights its potential for real-time bile acid analysis during liver transplantation procedures. SignificanceOur findings underscore the efficacy of NEVLP in tandem with advanced bile acid analysis methods as a reliable strategy for pre-transplant assessments of organ viability, potentially increasing the use of ECD organs and reducing organ shortages. The ability to monitor bile acid profiles in real-time provides crucial insights into liver function and ischemic injury, making significant strides in improving transplant outcomes and patient survival rates.

Optimal strategies for prevention of ischemia‑reperfusion injury in heart transplantation with prolonged cold ischemia time (review)

The shortage of organs for transplant remains a major challenge in transplantology. Transporting donor organs over long distances increases cold ischemia time, which is a risk factor for ischemia-reperfusion injury (IRI). In the face of critical shortages, the method and timing of organ preservation are crucial in increasing the donor pool. This paper examines the approaches, benefits, and drawbacks of organ preservation techniques used around the world.

Impact of controlled hypothermic preservation on outcomes following heart transplantation

BackgroundSevere primary graft dysfunction (PGD) is a major cause of early mortality after heart transplant. but the impact of donor organ preservation conditions on severity of PGD and survival have not been well characterized. MethodsData from US adult heart-transplant recipients in the GUARDIAN-Heart registry (NCT04141605) were analyzed to quantify PGD severity (stratified by ISHLT definition), mortality, and associated risk factors. The independent contributions of organ-preservation method (traditional ice storage versus controlled hypothermic preservation) and ischemic time were analyzed using propensity matching and logistic regression. ResultsAmong 1,061 US adult heart transplants performed between October 2015 and December 2022, controlled hypothermic preservation was associated with a significant reduction in the incidence of severe PGD compared to ice (6.6% (37/559) versus 10.4% (47/452), p=0.039). Following propensity matching, severe PGD was reduced by 50% (6.0% (17/281) versus 12.1% (34/281) respectively; p=0.018). The Kaplan-Meier terminal probability of 1-year mortality was 4.2% for recipients without PGD, 7.2% for mild or moderate PGD, and 32.1%, for severe PGD (p<0.001). The probability of severe PGD increased for both cohorts with longer ischemic time, but donor hearts stored on ice were more likely to develop severe PGD at all ischemic times compared to controlled hypothermic preservation. ConclusionsSevere PGD is the deadliest complication of heart transplantation and is associated with a 7.8-fold increase in probability of 1-year mortality. Controlled hypothermic preservation significantly attenuates the risk of severe PGD and is a simple yet highly effective tool for mitigating post-transplant morbidity.

The role of oxygenation in kidney and liver machine perfusion

Background. Organ transplantation is the optimal decision for patients in the end stage of many diseases. Certain conditions are required for the transportation and preservation of a donor organ after explantation, including factors such as temperature, pressure, and preservative solution. All currently available methods of preservation of donor organs are aimed at maximizing the complete preservation of the functional state of the graft from the moment of its removal to implantation and reperfusion in the recipient's body.Aim. The purpose of this review is to provide up-to-date information on the results of the studies performed in order to decide on the preferred method of organ preservation.Material and methods. An analysis of literature sources in English and Russian from 2009 to 2023 on this topic was performed in the databases PubMed, MEDLINE, Google Scholar. The review highlights the results of preclinical (on animal models) and clinical studies, as well as achievements in the field of ex-vivo machine perfusion with an emphasis on machine hypothermic perfusion and modified oxygenated hypothermic machine perfusion, subnormothermic machine perfusion and machine normothermic perfusion.Results. The daily increase in the number of patients in need of organ transplantation delays the timely selection and search for a donor. Organ donation after cardiac death is a promising step in an attempt to overcome the disbalance between the number of patients and organs, but the risk of developing early graft damage increases. The criteria for selecting donors and donor organs are being expanded, as a result, elderly donors and not-optimal grafts are included, but they are less resistant to ischemic damage. In this connection, there is a need for long-term infusion support through machine perfusion.Conclusion. In recent years, research has focused on alternative preservation methods, studying hypothermic, subnormothermic and normothermic machine perfusion. The use of machine perfusion has become the most widespread among kidney transplants and has shown good results. Further development is expected in the field of studying and improving this method of organ preservation, which allows not only transporting, but also improving the functional state of the graft.

#2556 BIOLOGICAL EFFECTS OF A SHORT PERIOD OF NORMOTHERMIC MACHINE PERFUSION IN MARGINAL KIDNEYS: RESULTS OF A PROTEOMICS ANALYSIS

Abstract Background and Aims Renal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35–37°C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, the biological effects of this technique on the marginal kidneys are uncertain. We consequently used mass spectrometry to define the proteomic profile of kidney tissue and urine from eight organs, considered unsuitable for transplantation, reconditioned for 120 min using a Kidney Assist device. Method Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine was collected at T0, T30, T60, and T120. Multiple algorithms, support vector machine (SVM) learning and partial least squares discriminant analysis (PLS-DA) were used to select the most discriminative proteins during NMP. Results Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 in kidney tissue during NMP. Machine learning algorithms recognized the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1, and F9) in the kidney and urine after NMP. Functional analysis showed that the most upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins were involved in the complement system and coagulation cascade. Results were, then, validated by classical and highly conservative biomolecular lab techniques. Conclusion Our proteomic analysis revealed that even brief periods of NMP induce substantial metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic.

Cryopreservation of tissues and organs: present, bottlenecks, and future.

Tissue and organ transplantation continues to be an effective measure for saving the lives of certain critically ill patients. The organ preservation methods that are commonly utilized in clinical practice are presently only capable of achieving short-term storage, which is insufficient for meeting the demand for organ transplantation. Ultra-low temperature storage techniques have garnered significant attention due to their capacity for achieving long-term, high-quality preservation of tissues and organs. However, the experience of cryopreserving cells cannot be readily extrapolated to the cryopreservation of complex tissues and organs, and the latter still confronts numerous challenges in its clinical application. This article summarizes the current research progress in the cryogenic preservation of tissues and organs, discusses the limitations of existing studies and the main obstacles facing the cryopreservation of complex tissues and organs, and finally introduces potential directions for future research efforts.

Complex treatment options of hip osteoarthritis

Osteoarthritis has the highest prevalence among the musculoskeletal diseases in all economically developed countries. Despite the improvement of diagnostic and treatment methods, the number of patients with osteoarthritis is increasing. The number of cases of newly diagnosed osteoarthritis, cases of disease progression and subsequent disability are also growing. There are many guidelines for treatment of osteoarthritis, however, specialists have no consensus, especially regarding the amount and duration of conservative therapy.&#x0D; The aim of the study was to analyze publications providing complex treatment options of hip osteoarthritis.&#x0D; A systematic literature review has been conducted by means of the open acccess Pub-Med/MEDLINE database and eLibrary search for the period until January 2022. The search depth was 20 years and was performed by keywords and phrases: hip joint osteoarthritis, conservative treatment, minimally invasive surgery, total hip arthroplasty.&#x0D; Unfortunately, the screening criteria for patients with osteoarthritis for total hip arthroplasty are not developed. The review analyzes the options of conservative therapy and minimally invasive surgical treatment for patients with osteoarthritis as the opportunity to avoid or delay the total hip replacement. The hip arthroplasty is not considered the gold standard; joint decision on surgery based on a comprehensive approach is made only when all the possibilities of conservative therapy are exhausted.&#x0D; It is widely believed that complex treatment using modern conservative and organ-preserving methods is the most common strategy for managing osteoarthritis of the hip joint. This approach improves clinical and functional condition of patients and slows down the progression of the disease.

Proteomics reveals specific biological changes induced by the normothermic machine perfusion of donor kidneys with a significant up-regulation of Latexin

Renal normothermic machine perfusion (NMP) is an organ preservation method based on the circulation of a warm (35–37 °C) perfusion solution through the renal vasculature to deliver oxygen and nutrients. However, its biological effects on marginal kidneys are unclear. We therefore used mass spectrometry to determine the proteomic profile of kidney tissue and urine from eight organs reconditioned for 120 min using a Kidney Assist device. Biopsies were taken during the pre-implantation histological evaluation (T-1), at the start of back table preparation (T0), and after 60 and 120 min of perfusion (T60, T120). Urine samples were collected at T0 (urine produced in the first 15 min after the beginning of normothermic reperfusion), T30, T60 and T120. Multiple algorithms, support vector machine learning and partial least squares discriminant analysis were used to select the most discriminative proteins during NMP. Statistical analysis revealed the upregulation of 169 proteins and the downregulation of 196 during NMP. Machine learning algorithms identified the top 50 most discriminative proteins, five of which were concomitantly upregulated (LXN, ETFB, NUDT3, CYCS and UQCRC1) and six downregulated (CFHR3, C1S, CFI, KNG1, SERPINC1 and F9) in the kidney and urine after NMP. Latexin (LXN), an endogenous carboxypeptidase inhibitor, resulted the most-upregulated protein at T120, and this result was confirmed by ELISA. In addition, functional analysis revealed that the most strongly upregulated proteins were involved in the oxidative phosphorylation system and ATP synthesis, whereas the downregulated proteins represented the complement system and coagulation cascade. Our proteomic analysis demonstrated that even brief periods of NMP induce remarkable metabolic and biochemical changes in marginal organs, which supports the use of this promising technique in the clinic.

Novel Polymerized Human Serum Albumin For Ex Vivo Lung Perfusion.

Ex vivo lung perfusion (EVLP) is a method of organ preservation to expand the donor pool by allowing organ assessment and repair. Perfusion solution composition is crucial to maintaining and improving organ function during EVLP. EVLP compared perfusates supplemented with either polymeric human serum albumin (PolyHSA) or standard human serum albumin (HSA). Rat heart-lung blocks underwent normothermic EVLP (37°C) for 120 minutes using perfusate with 4% HSA or 4% PolyHSA synthesized at a 50:1 or 60:1 molar ratio of glutaraldehyde to PolyHSA. Oxygen delivery, lung compliance, pulmonary vascular resistance (PVR), wet-to-dry ratio, and lung weight were measured. Perfusion solution type (HSA or PolyHSA) significantly impacted end-organ metrics. Oxygen delivery, lung compliance, and PVR were comparable among groups (P > 0.05). Wet-to-dry ratio increased in the HSA group compared to the PolyHSA groups (both P < 0.05) suggesting edema formation. Wet-to-dry ratio was most favorable in the 60:1 PolyHSA-treated lungs compared to HSA (P < 0.05). Compared to using HSA, PolyHSA significantly lessened lung edema. Our data confirm that the physical properties of perfusate plasma substitutes significantly impact oncotic pressure and the development of tissue injury and edema. Our findings demonstrate the importance of perfusion solutions and PolyHSA is an excellent candidate macromolecule to limit pulmonary edema.

Ex Vivo Gene Delivery to Porcine Cardiac Allografts Using a Myocardial-Enhanced Adeno-Associated Viral Vector.

Transplantation, the gold standard intervention for organ failure, is a clinical field that is ripe for applications of gene therapy. One of the major challenges in applying gene therapy to this field is the need for a method that achieves consistent and robust gene delivery to allografts. Normothermic ex vivo perfusion is a growing organ preservation method and a device for cardiac preservation was recently approved by the Food and Drug Administration (FDA) (Organ Care System, OCS™; TransMedics, Inc., Andover, MA); this device maintains donor hearts in a near physiologic state while they are transported from the donor to the recipient. This study describes the administration of recombinant adeno-associated viral vectors (rAAVs) during ex vivo normothermic perfusion for the delivery of transgenes to porcine cardiac allografts. We utilized a myocardial-enhanced AAV3b variant, SASTG, assessing its transduction efficiency in the OCS perfusate relative to other AAV serotypes. We describe the use of normothermic ex vivo perfusion to deliver SASTG carrying the Firefly Luciferase transgene to porcine donor hearts in four heterotopic transplant procedures. Durable and dose-dependent transgene expression was achieved in the allografts in 30 days, with no evidence of off-target transgene expression. This study demonstrates the feasibility and efficiency of delivering genes to a large animal allograft utilizing AAV vectors during ex vivo perfusion. These findings support the idea of gene therapy interventions to enhance transplantation outcomes.

The international experience of in-situ recovery of the DCD heart: a multicentre retrospective observational study

Heart transplantation is an effective treatment offering the best recovery in both quality and quantity of life in those affected by refractory, severe heart failure. However, transplantation is limited by donor organ availability. The reintroduction of heart donation after the circulatory determination of death (DCD) in 2014 offered an uplift in transplant activity by 30%. Thoraco-abdominal normothermic regional perfusion (taNRP) enables in-situ reperfusion of the DCD heart. The objective of this paper is to assess the clinical outcomes of DCD donor hearts recovered and transplanted from donors undergoing taNRP. This was a multicentre retrospective observational study. Outcomes included functional warm ischaemic time, use of mechanical support immediately following transplantation, perioperative and long-term actuarial survival and incidence of acute rejection requiring treatment. 157 taNRP DCD heart transplants, performed between February 2, 2015, and July 29, 2022, have been included from 15 major transplant centres worldwide including the UK, Spain, the USA and Belgium. 673 donations after the neurological determination of death (DBD) heart transplantations from the same centres were used as a comparison group for survival. taNRP resulted in a 23% increase in heart transplantation activity. Survival was similar in the taNRP group when compared to DBD. 30-day survival was 96.8% ([92.5%-98.6%] 95% CI, n=156), 1-year survival was 93.2% ([87.7%-96.3%] 95% CI, n=72) and 5-year survival was 84.3% ([69.6%-92.2%] 95% CI, n=13). Our study suggests that taNRP provides a significant boost to heart transplantation activity. The survival rates of taNRP are comparable to those obtained for DBD transplantation in this study. The similar survival may in part be related to a short warm ischaemic time or through a possible selection bias of younger donors, this being an uncontrolled observational study. Therefore, our study suggests that taNRP offers an effective method of organ preservation and procurement. This early success of the technique warrants further investigation and use. None of the authors have a financial relationship with a commercial entity that has an interest in the subject.

Biliary Metabolome Profiling for Evaluation of Liver Metabolism and Biliary Tract Function Related to Organ Preservation Method and Degree of Ischemia in a Porcine Model.

The development of surgical techniques, immunosuppressive strategies and new organ preservation methods have meant that transplant centers have to face the problem of an insufficient number of organs for transplantation concerning the constantly growing demand. Therefore, using organs from expanded criteria donors and developing new analytical solutions to find parameters or compounds that would allow a more efficient assessment of organ quality before transplantation are options for meeting this challenge. This study proposed bile metabolomic analysis to evaluate liver metabolism and biliary tract function depending on the organ preservation method and degree of warm ischemia time. The analyses were performed on solid-phase microextraction-prepared bile samples from porcine model donors with mild (heart beating donor [HBD]) and moderate warm ischemia (donation after circulatory death [DCD]) grafts subjected to static cold storage (SCS) or normothermic ex vivo liver perfusion (NEVLP) before transplantation. Bile produced in the SCS-preserved livers was characterized by increased levels of metabolites such as chenodeoxycholic acid, arachidonic acid and 5S-hydroxyeicosatetraeonic acid, as well as saturated and monounsaturated lysophosphatidylcholines (LPC). Such changes may be associated with differences in the bile acid synthesis pathways and organ inflammation. Moreover, it has been shown that NEVLP reduced the negative effect of ischemia on organ function. A linear relationship was observed between levels of lipids from the LPC group and the time of organ ischemia. This study identified metabolites worth considering as potential markers of changes occurring in preserved grafts.

Morphological justification of organ-preserving methods of surgical treatment of patients with liver echinococcosis

The purpose of the research is the study of the morphological structure of echinococcal cysts to assess the possibility of using organ-preserving methods of surgical treatment.Materials and methods. A clinical, instrumental, and morphological fundamental study was performed in the Surgical Clinic of the Botkin Hospital when radiation and morphological data in addition to clinical data were studied for 28 patients who underwent surgical treatment for liver echinococcosis. Excised gross specimens were examined to study the capsule structure, and the penetration of germinal elements of the cysts through membranes of the parasite (64 successively excised primary operated echinococcal cysts).Results and discussion. The fibrous capsule of the echinococcal cyst is a good barrier against Protoscolexes penetrating into the liver tissue. None of the 64 specimens studied in detail was found to have germinal elements of any echinococcal cyst penetrating through its fibrous capsule. The morphological justification of organ-preserving methods in the treatment of patients with liver echinococcosis allows a conclusion that these interventions are safe and radical.

РЕПРОДУКТИВНОЕ ЗДОРОВЬЕ ЖЕНЩИНЫ ПОСЛЕ УСПЕШНОЙ ЭМБОЛИЗАЦИИ СОСУДОВ МАТКИ И МАЛОГО ТАЗА ПРИ РАЗВИТИИ АКУШЕРСКОГО КРОВОТЕЧЕНИЯ В АНАМНЕЗЕ

Bleeding during pregnancy and childbirth is one of the leading causes of maternal mortality. An effective organ-preserving method of treating uncontrolled obstetric bleeding is uterine artery embolization (EMA). The advantages of EMA are the ease of determining the place of bleeding, reducing repeated bleeding from the collaterals, preserving the uterus and, consequently, fertility.

Benign intrauterine diseases in post menopause. Organ-preserving methods of treatment

Benign intrauterine diseases in post menopause. Organ-preserving methods of treatment

ADD10 protects renal cells from cold injuries by improving energy metabolism

Static cold storage (SCS) is currently the most widely used method for organ preservation, but a number of limitations are associated including tissue damage and restricted opportunity for organ repair. Thus, the development of improved hypothermic storage solutions is an urgent need. Herein, using a renal epithelial cell model (LLC-PK1), we tested the benefits of ADD10, a novel clinical grade antioxidant product, in reducing damages associated with ischemia-reperfusion (IR). Cells were stored up to 24h at 4 °C in University of Wisconsin (UW) solution without or in the presence of 1% ADD10 with following reperfusion up to 24h at 37 °C. The presence of ADD10 significantly decreased cells damages, cell death, and the level of reactive oxygen species (ROS) (P < 0.05). Concomitantly, ADD10 supplementation also favored an increased oxygen consumption rate (OCR) and improved bioenergetics of LLC-PK1 cells (P < 0.05). Finally, preliminary in vivo studies suggested a benefit of ADD10 on the renal function post-transplantation. In conclusion, these results demonstrate that the addition of ADD10 to the preservation solution not only efficiently protects renal cells during SCS, but also improves the functionality of cold-stored organs during transplantation.

MODERN METHODS OF SURGICAL TREATMENT FOR PLACENTA ACCRETA

Nowadays obstetrics practice shows a significant increase in the incidence of true placenta ingrowth ― a severe obstetric pathology accompanied by a high risk of massive bleeding and maternal mortality. Therefore, the delivery of such patients was earlier accompanied by organ-resection operations, followed by inability to fulfill the reproductive function. Therefore, it is topical to search for organ-preserving methods of operative delivery of patients with this pathology. This approach will allow preserving the menstrual and, possibly, childbearing function.

Is the Organ Care System (OCS) Still the First Choice With Emerging New Strategies for Donation After Circulatory Death (DCD) in Heart Transplant?

The scarcity of donor hearts continues to be a challenge in transplants for advanced heart failure patients. With an increasing number of patients on the waiting list for a heart transplant, the discrepancy in the number between donors and recipients is gradually increasing and poses a new challenge that plagues the healthcare systems when it comes to the heart. Several technologies have been developed to expand the donor pool in recent years. One such method is the organ care system (OCS). The standard method of organ preservation is the static cold storage (SCS) method which allows up to four hours of safe preservation of the heart. However, beyond four hours of cold ischemia, the incidence of primary graft dysfunction increases significantly. OCS keeps the heart perfused close to the physiological state beyond the four hours with superior results, which allows us to travel further and longer distances, leading to expansion in the donor pool. In this review, we discuss the OCS system, its advantages, and shortcomings.

The Immunological Effect of Oxygen Carriers on Normothermic Ex Vivo Liver Perfusion.

IntroductionNormothermic ex vivo liver perfusion (NEVLP) is an organ preservation method that allows liver graft functional assessment prior to transplantation. One key component of normothermic perfusion solution is an oxygen carrier to provide oxygen to the liver to sustain metabolic activities. Oxygen carriers such as red blood cells (RBCs) or hemoglobin-based oxygen carriers have an unknown effect on the liver-resident immune cells during NEVLP. In this study, we assessed the effects of different oxygen carriers on the phenotype and function of liver-resident immune cells.MethodsAdult Lewis rat livers underwent NEVLP using three different oxygen carriers: human packed RBCs (pRBCs), rat pRBCs, or Oxyglobin (a synthetic hemoglobin-based oxygen carrier). Hourly perfusate samples were collected for downstream analysis, and livers were digested to isolate immune cells. The concentration of common cytokines was measured in the perfusate, and the immune cells underwent phenotypic characterization with flow cytometry and quantitative reverse transcription polymerase chain reaction (qRT-PCR). The stimulatory function of the liver-resident immune cells was assessed using mixed lymphocyte reactions.ResultsThere were no differences in liver function, liver damage, or histology between the three oxygen carriers. qRT-PCR revealed that the gene expression of nuclear factor κ light chain enhancer of activated B cells (NF-kB), Interleukin (IL-1β), C-C motif chemokine ligand 2 (CCL2), C-C motif chemokine ligand 7 (CCL7), and CD14 was significantly upregulated in the human pRBC group compared with that in the naive, whereas the rat pRBC and Oxyglobin groups were not different from that of naive. Flow cytometry demonstrated that the cell surface expression of the immune co-stimulatory protein, CD86, was significantly higher on liver-resident macrophages and plasmacytoid dendritic cells perfused with human pRBC compared to Oxyglobin. Mixed lymphocyte reactions revealed increased allogeneic T-cell proliferation in the human and rat pRBC groups compared to that in the Oxyglobin group.ConclusionsLiver-resident immune cells are important mediators of rejection after transplantation. In this study, we show that the oxygen carrier used in NEVLP solutions can affect the phenotype of these liver-resident immune cells. The synthetic hemoglobin-based oxygen carrier, Oxyglobin, showed the least amount of liver-resident immune cell activation and the least amount of allogeneic proliferation when compared to human or rat pRBCs. To mitigate liver-resident immune cell activation during NEVLP (and subsequent transplantation), Oxyglobin may be an optimal oxygen carrier.