Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model

Rigo, Federica; Stefano, Nicola De; Navarro-Tableros, Víctor; David, Ezio; Rizza, Giorgia; Catalano, Giorgia; Gilbo, Nicholas; Maione, Francesca; Gonella, Federica; Roggio, Dorotea; Martini, Silvia; Patrono, Damiano; Salizzoni, Mauro; Camussi, Giovanni; Romagnoli, Renato

doi:10.1097/tp.0000000000002123

Cited by 77 publications

(71 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, Banan et al used a dialyzer to maintain the perfusate pH and electrolyte profiles within physiologic ranges throughout the 8‐hour NEVLP of human liver grafts . Rigo et al recently reported on escalating transaminase release during 4 hours of normothermic perfusion of rat livers without dialysis, resulting in significant damage of the liver architecture …”

Section: Discussionmentioning

confidence: 99%

“…However Original article | 285 without dialysis, resulting in significant damage of the liver architecture. (31) Kupffer cell-dependent signaling causes a hypermetabolic state with increased oxygen consumption and glycogen depletion in hepatocytes and reduced transplant survival in rats. (32,33) These mechanisms may contribute to increased susceptibility to ischemia/reperfusion injury of ECD liver grafts because preexisting conditions have already aggravated microcirculation and energy expenditure.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

et al. 2019

View full text Add to dashboard Cite

Normothermic ex vivo liver machine perfusion might be a superior preservation strategy for liver grafts from extended criteria donors. However, standardized small animal models are not available for basic research on machine perfusion of liver grafts. A laboratory‐scaled perfusion system was developed consisting of a custom‐made perfusion chamber, a pressure‐controlled roller pump, and an oxygenator. Male Wistar rat livers were perfused via the portal vein for 6 hours using oxygenated culture medium supplemented with rat erythrocytes. A separate circuit was connected via a dialysis membrane to the main circuit for plasma volume expansion. Glycine was added to the flush solution, the perfusate, and the perfusion circuit. Portal pressure and transaminase release were stable over the perfusion period. Dialysis significantly decreased the potassium concentration of the perfusate and led to significantly higher bile and total urea production. Hematoxylin‐eosin staining and immunostaining for single‐stranded DNA and activated caspase 3 showed less sinusoidal dilatation and tissue damage in livers treated with dialysis and glycine. Although Kupffer cells were preserved, tumor necrosis factor α messenger RNA levels were significantly decreased by both treatments. For proof of concept, the optimized perfusion protocol was tested with donation after circulatory death (DCD) grafts, resulting in significantly lower transaminase release into the perfusate and preserved liver architecture compared with baseline perfusion. In conclusion, our laboratory‐scaled normothermic portovenous ex vivo liver perfusion system enables rat liver preservation for 6 hours. Both dialysis and glycine treatment were shown to be synergistic for preservation of the integrity of normal and DCD liver grafts.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Extracellular vesicles from human liver stem cells reduce injury in an ex-vivo normo-thermic hypoxic rat liver perfusion model [33]. Extracellular vesicles from human liver stem cells reduce injury in an ex-vivo normo-thermic hypoxic rat liver perfusion model [33].…”

Section: Immune Cell Diseasesmentioning

confidence: 99%

“…EVs also operate in tissue pathology. Extracellular vesicles from human liver stem cells reduce injury in an ex-vivo normo-thermic hypoxic rat liver perfusion model [33]. In the lung, anti-inflammatory EVs addressed to alveolar macrophages result in the protection of epithelial cells [34].…”

Section: Immune Cell Diseasesmentioning

confidence: 99%

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Meldolesi

2019

Clinical and Experimental Immunology

View full text Add to dashboard Cite

Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar, thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs. The EV physiology of the various immune cells differs as expected from their differential properties. Some properties, however, are common: EV release, taking place already at rest, is greatly increased upon cell stimulation; extracellular navigation occurs adjacent and at distance from the releasing cells; binding to and uptake by target cells are specific. EVs received from other immune or distinct cells govern many functions in target cells. Immune diseases in which EVs play multiple, often opposite (aggression and protection) effects, are numerous; inflammatory diseases; pathologies of various tissues; and brain diseases, such as multiple sclerosis. EVs also have effects on interactive immune and cancer cells. These effects are often distinct, promoting cytotoxicity or proliferation, the latter together with metastasis and angiogenesis. Diagnoses depend on the identification of EV biomarkers; therapies on various mechanisms such as (1) removal of aggression-inducing EVs; (2) EV manipulations specific for single targets, with insertion of surface peptides or luminal miRNAs; and (3) removal or re-expression of molecules from target cells.

show abstract

“…Delivery of therapeutic molecules in the perfusate has been investigated including high-dose antibiotics for treatment of contamination or donor infection, delivery of antiinflammatory drugs, and stem cell-derived extracellular vesicles. 64,114 Recently, Goldaracena et al 115 investigated the efficacy of administering miravirsen to inhibit miR-122 function and induce hepatitis C (HCV) resistance in porcine livers on NMP. Hepatitis C patients receiving transplants experience acute reinfection upon reperfusion, which is often more severe and leads to cirrhosis of the liver in up to 30% of patients within five years.…”

Section: Livermentioning

confidence: 99%

Bioengineering approaches to organ preservation ex vivo

Pinezich

Vunjak‐Novakovic

2019

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

The advent of successful solid organ transplantation is undoubtedly among the most significant medical achievements of the 20th century. Despite advances in the field of transplantation since its inception over 50 years ago, our approach to donor organ preservation outside of the body remains unchanged. Recently, attempts have been made to replace static cold storage with more sophisticated ex vivo machine perfusion. Rather than cooling the organ on ice to slow metabolic processes, machine perfusion aims to support normal metabolic function in a near-physiologic environment and to provide a platform on which the organ can be evaluated, preserved, and recovered. Ex vivo machine perfusion devices have demonstrated early success with respect to transplant outcomes in heart, lung, and liver, with perfusion times limited to several hours. The continued development of more advanced perfusion systems is likely to extend the duration of ex vivo organ support to days or even weeks, and enable recovery of initially unsuitable donor organs. In this review, we discuss recent clinical and pre-clinical studies, state-of-the-art organ preservation technologies, existing limitations, and a perspective on future developments.

show abstract

Extracellular Vesicles from Human Liver Stem Cells Reduce Injury in an Ex Vivo Normothermic Hypoxic Rat Liver Perfusion Model

Abstract: HLSC-EV treatment, even in a short-duration model, was feasible and effectively reduced liver injury during hypoxic NMP.

Cited by 77 publications

References 29 publications

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

Improvement of Normothermic Ex Vivo Machine Perfusion of Rat Liver Grafts by Dialysis and Kupffer Cell Inhibition With Glycine

Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Bioengineering approaches to organ preservation ex vivo

Contact Info

Product

Resources

About