Evlp

Ex-vivo lung perfusion (EVLP) has extended the number of transplantable lungs by reconditioning marginal organs. However, EVLP is performed at 37°C without homeostatic regulation leading to metabolic wastes' accumulation in the perfusate and, as a corrective measure, the costly perfusate is repeatedly replaced during the standard of care procedure. As an interesting alternative, a hemodialyzer could be placed on the EVLP circuit, which was previously shown to rebalance the perfusate composition and to maintain lung function and viability without appearing to impact the global gene expression in the lung...

Primary graft dysfunction (PGD) is a common complication after lung transplantation. A plethora of contributing factors are known and assessment of donor lung function prior to organ retrieval is mandatory for determination of lung quality. Specialized centers increasingly perform ex vivo lung perfusion (EVLP) to further assess lung functionality and improve and extend lung preservation with the aim to increase lung utilization. EVLP can be performed following different protocols. The impact of the individual EVLP parameters on PGD development, organ function and postoperative outcome remains to be fully investigated...

OBJECTIVE: Donation after circulatory death (DCD) donors offer the ability to expand the lung donor pool and ex vivo lung perfusion (EVLP) further contributes to this ability by allowing for additional evaluation and resuscitation of these extended criteria donors. We sought to determine the outcomes of recipients receiving organs from DCD EVLP donors in a multi-center setting. METHODS: This was an unplanned post-hoc analysis of a multicenter, prospective, non-randomized trial that took place in 2011-2017 with 3-years of follow up...

Chinese Hamster Ovary (CHO) cells, employed primarily for manufacturing monoclonal antibodies and other recombinant protein (r-protein) therapeutics, are emerging as a promising host for vaccine antigen production. This is exemplified by the recently approved CHO cell-derived subunit vaccines (SUV) against respiratory syncytial virus (RSV) and varicella-zoster virus (VZV), as well as the enveloped virus-like particle (eVLP) vaccine against hepatitis B virus (HBV). Here, we summarize the design, production, and immunogenicity features of these vaccine and review the most recent progress of other CHO-derived vaccines in pre-clinical and clinical development...

Indications for ex vivo lung perfusion (EVLP) have evolved from assessment of questionable donor lungs to treatment of some pathologies and the logistics. Yet up to 3 quarters of donor lungs remain discarded across the globe. Multiday preservation of discarded human lungs on EVLP platforms would improve donor lung utilization rates via application of sophisticated treatment modalities, which could eventually result in zero waitlist mortality. The purpose of this article is to summarize advances made on the technical aspects of the protocols in achieving a stable multiday preservation of isolated EVLP...

With the ongoing shortage of donor lungs, ex vivo lung perfusion (EVLP) offers the opportunity for objective assessment and potential therapeutic repair of marginal organs. There is a need for robust research on EVLP interventions to increase the number of transplantable organs. The use of human lungs, which have been declined for transplant, for these studies is preferable to animal organs and is indeed essential if clinical translation is to be achieved. However, experimental human EVLP is time-consuming and expensive, limiting the rate at which promising interventions can be assessed...

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Volatile anesthetics have been shown in different studies to reduce ischemia reperfusion injury (IRI). Ex vivo lung perfusion (EVLP) facilitates graft evaluation, extends preservation time and potentially enables injury repair and improvement of lung quality. We hypothesized that ventilating lungs with sevoflurane during EVLP would reduce lung injury and improve lung function. We performed a pilot study to test this hypothesis in a slaughterhouse sheep DCD model. Lungs were harvested, flushed and stored on ice for 3 h, after which EVLP was performed for 4 h...

Personalized cancer vaccines based on resected tumors from patients is promising to address tumor heterogeneity to inhibit tumor recurrence or metastasis. However, it remains challenge to elicit immune activation due to the weak immunogenicity of autologous tumor antigens. Here, a hybrid membrane cancer vaccine is successfully constructed by membrane fusion to enhance adaptive immune response and amplify personalized immunotherapy, which formed a codelivery system for autologous tumor antigens and immune adjuvants...

Engineering donor organs to better tolerate the harmful non-immunological and immunological responses inherently related to solid organ transplantation would improve transplant outcomes. Our enhanced knowledge of ischemia-reperfusion injury, alloimmune responses and pathological fibroproliferation after organ transplantation, and the advanced toolkit available for gene therapies, have brought this goal closer to clinical reality. Ex vivo organ perfusion has evolved rapidly especially in the field of lung transplantation, where clinicians routinely use ex vivo lung perfusion (EVLP) to confirm the quality of marginal donor lungs before transplantation, enabling safe transplantation of organs originally considered unusable...

BACKGROUND: Ex vivo lung perfusion (EVLP) is a useful tool for assessing lung grafts quality before transplantation. Studies indicate that donor sex is as an important factor for transplant outcome, as females present higher inflammatory response to brain death (BD) than males. Here, we investigated sex differences in the lungs of rats subjected to BD followed by EVLP. METHODS: Male and female Wistar rats were subjected to BD, and as controls sham animals. Arterial blood was sampled for gas analysis...

Normothermic ex vivo lung perfusion (EVLP) can resuscitate marginal lung allografts to increase organs available for transplantation. During normothermic perfusion, cellular metabolism is more active compared with subnormothermic perfusion, creating a need for an oxygen (O2) carrier in the perfusate. As an O2 carrier, red blood cells (RBCs) are a scarce resource and are susceptible to hemolysis in perfusion circuits, thus releasing cell-free hemoglobin (Hb), which can extravasate into the tissue space, thus promoting scavenging of nitric oxide (NO) and oxidative tissue damage...

BACKGROUND: Ex vivo lung perfusion (EVLP) is an advanced platform for isolated lung assessment and treatment. Radiographs acquired during EVLP provide a unique opportunity to assess lung injury. The purpose of our study was to define and evaluate EVLP radiographic findings and their association with lung transplant outcomes. METHODS: We retrospectively evaluated 113 EVLP cases from 2020-21. Radiographs were scored by a thoracic radiologist blinded to outcome. Six lung regions were scored for 5 radiographic features (consolidation, infiltrates, atelectasis, nodules, and interstitial lines) on a scale of 0 to 3 to derive a score...

Prime editing enables precise installation of genomic substitutions, insertions and deletions in living systems. Efficient in vitro and in vivo delivery of prime editing components, however, remains a challenge. Here we report prime editor engineered virus-like particles (PE-eVLPs) that deliver prime editor proteins, prime editing guide RNAs and nicking single guide RNAs as transient ribonucleoprotein complexes. We systematically engineered v3 and v3b PE-eVLPs with 65- to 170-fold higher editing efficiency in human cells compared to a PE-eVLP construct based on our previously reported base editor eVLP architecture...

INTRODUCTION: Cytomegalovirus (CMV) is the most common cause of congenital infection and affected children often have permanent neurodevelopmental sequelae, including hearing loss and intellectual disability. Vaccines to prevent transmission of CMV during pregnancy are a public health priority. This first-in-humans dose-ranging, randomized, placebo-controlled, observer-blinded study evaluated the safety and immunogenicity of an enveloped virus-like particle (eVLP) vaccine expressing a modified form of the CMV glycoprotein B (gB)...

BACKGROUND: This study compared utilization and outcomes of the two widely utilized ex vivo lung perfusion (EVLP) platforms in the United States (US): a static platform and a portable platform. METHODS: Adult (≥18 years) bilateral lung-only transplants utilizing EVLP between 2/28/2018-12/31/2022 in the United Network for Organ Sharing database were included. Pre-discharge acute rejection, intubation at 72 hours post-transplant, extracorporeal membrane oxygenation (ECMO) at 72 hours post-transplant, primary graft dysfunction grade 3 (PGD3) at 72 hours post-transplant, 30-day mortality, and 1-year mortality were evaluated using multivariable regressions...

BACKGROUND: In yeast, recombinant membrane proteins including viral scaffold proteins used for the formation of enveloped Virus-like particles (eVLPs) typically accumulate intracellularly. Their recovery is carried out by mechanical disruption of the cells, often in combination with detergent treatment. Cell permeabilization is an attractive alternative to mechanical lysis because it allows for milder and more selective recovery of different intracellular products. RESULTS: Here, we present a novel approach for extraction of integral membrane proteins from yeast based on cell envelope permeabilization through a combination of pulsed electric field and lytic enzyme pretreatment of the cells...

Cancer, a prevalent disease posing significant threats to human health and longevity, necessitates effective therapeutic interventions. Chemotherapy has emerged as a primary strategy following surgical procedures for combating most malignancies. Despite the considerable efficacy of conventional chemotherapeutic agents against cancer cells, their utility is hindered by profound challenges such as multidrug resistance and deleterious toxic side effects, thereby limiting their systemic application. To tackle these challenges, we have devised a promising nanomedicine platform based on a plant virus...

INTRODUCTION: In recent years, the field of graft preservation has made considerable strides in improving outcomes related to solid organ restoration and regeneration. Ex vivo lung perfusion (EVLP) in line with the related devices and treatments has yielded promising results within preclinical and clinical studies, with the potential to improve graft quality. Its main benefit is to render marginal and declined donor lungs suitable for transplantation, ultimately increasing the donor pool available for transplantation...

BACKGROUND: Ischemia-reperfusion injury is a key complication following lung transplantation. The clinical application of ex vivo lung perfusion (EVLP) to assess donor lung function has significantly increased the utilization of "marginal" donor lungs with good clinical outcomes. The potential of EVLP on improving organ quality and ameliorating ischemia-reperfusion injury has been suggested. METHODS: To determine the effects of ischemia-reperfusion and EVLP on gene expression in human pulmonary microvascular endothelial cells and epithelial cells, cell culture models were used to simulate cold ischemia (4 °C for 18 h) followed by either warm reperfusion (DMEM + 10% FBS) or EVLP (acellular Steen solution) at 37 °C for 4 h...