Intraportal infusion of 99mtechnetium-macro-aggregrated albumin particles and hepatocytes in rabbits: assessment of shunting and portal hemodynamic changes

Schneider, Andrea; Attaran, Masoumeh; Gratz, K. F.; Bleck, Joerg S.; Winkler, Michael; Manns, Michael P.; Ott, Michael

doi:10.1097/01.tp.0000044454.43076.7b

Cited by 28 publications

(32 citation statements)

References 28 publications

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“…, digestive bleeding, liver tumors and hemodynamic disorders 11 . It has been shown that changes on the morphology of red blood cells may arise in the first hours after trauma, persists for several days and may interfere with the their labeling.…”

Section: Introductionmentioning

confidence: 99%

Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats

Carvalho¹,

Araújo‐Filho²,

Azevedo³

et al. 2011

Acta Cir. Bras.

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PURPOSE:To investigate the influence of partial colectomy associated with hepatectomy on the biodistribution of the 99m Tc-phytate, on metabolic parameters, as well as labeling and morphology of red blood cells. METHODS: Wistar rats were distributed into three groups (each with six), nominated as colectomy, colectomy+hepatectomy and sham. In the 30 th postoperative day all rats were injected with 99mTc-phytate 0.1mL i.v. (radioactivity 0.66 MBq). After 15 minutes, liver sample was harvested and weighed. Percentage radioactivity per gram of tissue (%ATI/g) was determined using an automatic gammacounter. Serum AST, ALT, alkaline phosphatase and red blood cells labeling were determined. RESULTS: The liver %ATI/g and red blood cells labeling were lower in colectomy and colectomy+hepatectomy rats than in sham rats (p <0.05), and no difference was detected comparing the colectomy and colectomy+hepatectomy groups. Red blood cells morphology did not differ among groups. Serum levels of AST, ALT and alkaline fosfatase were significantly higher in colectomy+hepatectomy than in colectomy rats (p<0.001). CONCLUSION: Hepatectomy associated with colectomy lowered the uptake of radiopharmaceutical in liver and in red blood cells in rats, coinciding with changes in liver enzymatic activity. Keywords: Colectomy. Hepatectomy. Metabolism. Biological Availability. Technetium. Rats. RESUMO OBJETIVO:Investigar a influência da colectomia associada à hepatectomia parcial, na biodistribuição do fitato99m TcO 4 , na marcação e morfologia de hemácias e em parâmetros metabólicos. MÉTODOS: Ratos Wistar foram distribuídos em três grupos (seis animais cada), denominados: colectomia, colectomia+hepatectomia e sham. No 30º dia pós-operatório, em todos eles foi feita injeção de 0,1 mL i.v. de fitato-

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Section: Introductionmentioning

confidence: 99%

Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats

Carvalho¹,

Araújo‐Filho²,

Azevedo³

et al. 2011

Acta Cir. Bras.

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“…However, one The use of primary or genetically modified primary hepatocytes offers new-generation therapeutic approaches, of the major limiting factors has been the low number of hepatocytes that can be efficiently infused into the including hepatocyte transplantation, in the treatment of various types of liver diseases (8,12,13,35,48). Clinically, liver without causing complications (i.e., 2-5% of the total number of viable hepatocytes of the host liver) isolated hepatocytes have been transplanted into the livers of more than 60 patients to provide a temporal bridge (15,35,46). Moreover, researchers have shown that only a fraction (10-20%) of the transplanted hepatocytes into until an orthotopic liver transplantation can be performed, in cases such as fulminant liver failure or as an improvethe liver is able to be engrafted in the liver parenchyma from the portal pedicles (19,28).…”

Section: Introductionmentioning

confidence: 99%

Genetic Modification of Hepatocytes towards Hepatocyte Transplantation and Liver Tissue Engineering

et al. 2006

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Cell-based therapies, including liver tissue engineering following hepatocyte transplantation, have therapeutic potential for several types of liver diseases. Modifications in the methodology to manipulate the donor hepatocytes in a more simple and timely manner prior to transplantation would enhance the therapeutic efficacy of this procedure. Conventional approach for vector-mediated gene transduction to the isolated hepatocytes has been performed under primary culture conditions that routinely require several days to complete. In our study, we have established a clinically feasible approach that requires only 1 h of infection time with an adenoviral vector system that results in an extremely efficient transduction efficiency (>80%). To optimize transduction efficiency and sustain normal cellular function, we determined that the isolated hepatocytes should be maintained in UW solution as a suspension medium and infected with adenoviral vectors (Ad) for no more than 1 h at a MOI of 1. To establish if the isolated hepatocytes could be used as a source for cell-based therapies, we transplanted the Ad-transduced hepatocytes into the liver or under the kidney capsule. When the cells were transplanted into the liver, Ad-transduced hepatocytes cultured in suspension conditions were found to have a significantly higher survival rate (p < 0.01) than Ad-transduced hepatocytes cultured under standard conditions. We also confirmed that these Ad-transduced hepatocytes have ability to survive long term and were able to engineer a biologically active hepatic tissue under the kidney capsule. Finally, we obtained high level of transduction into canine, porcine, and human isolated hepatocytes in a suspension solution mixed with Ad. In conclusion, the present studies demonstrate that isolated hepatocytes could be genetically modified using Ad when kept in a suspension solution. For this reason, this cellmodified technique could be used for the treatment of liver-targeted diseases and/or disorders.Key words: Hepatocyte transplantation; Gene modification; Ex vivo gene therapy; Adenoviral vector; Liver tissue engineering INTRODUCTIONmost of the cases, hepatocyte transplantation had been conducted by infusing cells into the liver through the portal vein or via the splenic circulation. However, one The use of primary or genetically modified primary hepatocytes offers new-generation therapeutic approaches, of the major limiting factors has been the low number of hepatocytes that can be efficiently infused into the including hepatocyte transplantation, in the treatment of various types of liver diseases (8,12,13,35,48). Clinically, liver without causing complications (i.e., 2-5% of the total number of viable hepatocytes of the host liver) isolated hepatocytes have been transplanted into the livers of more than 60 patients to provide a temporal bridge (15,35,46). Moreover, researchers have shown that only a fraction (10-20%) of the transplanted hepatocytes into until an orthotopic liver transplantation can be performed, in cases such as ...

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“…1,2 However, this approach of cell transplantation through the portal vein is limited in the number of cells that can be transplanted at one time because of potential life-threatening complications. 3,5,6 To increase the utility of hepatocyte-based therapy, it is important to develop a method that allows for the engraftment of a greater number of hepatocytes. In this context, transplanting hepatocytes at an extrahepatic site is attractive because it would provide additional space to maintain a greater number of cells, and with fewer complications.…”

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confidence: 99%

Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases

et al. 2005

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Liver tissue engineering using hepatocyte transplantation has been proposed as an alternative to whole-organ transplantation or liver-directed gene therapy to correct various types of hepatic insufficiency. Hepatocytes are not sustained when transplanted under the kidney capsule of syngeneic mice. However, when we transplanted hepatocytes with the extracellular matrix components extracted from Engelbreth-Holm-Swarm cells, hepatocytes survived for at least 140 days and formed small liver tissues. Liver engineering in hemophilia A mice reconstituted 5% to 10% of normal clotting activity, enough to reduce the bleeding time and have a therapeutic benefit. Conversely, the subcutaneous space did not support the persistent survival of hepatocytes with Engelbreth-Holm-Swarm gel matrix. We hypothesized that establishing a local vascular network at the transplantation site would reduce graft loss. To test this idea, we provided a potent angiogenic agent before hepatocyte transplantation into the subcutaneous space. With this procedure, persistent survival was achieved for the length of the experiment (120 days). To establish that these engineered liver tissues also retained their native regeneration potential in vivo, we induced two different modes of proliferative stimulus to the naïve liver and confirmed that hepatocytes within the extrahepatic tissues regenerated with activity similar to that of naïve liver. In conclusion, our studies indicate that liver tissues can be engineered and maintained at extrahepatic sites, retain their capacity for regeneration in vivo, and used to successfully treat genetic disorders. (HEPATOLOGY 2005; 41:132-140.)

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Intraportal infusion of 99mtechnetium-macro-aggregrated albumin particles and hepatocytes in rabbits: assessment of shunting and portal hemodynamic changes

Cited by 28 publications

References 28 publications

Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats

Metabolic and hematologic consequences of colectomy associated to hepatectomy in rats

Genetic Modification of Hepatocytes towards Hepatocyte Transplantation and Liver Tissue Engineering

Liver tissue engineering at extrahepatic sites in mice as a potential new therapy for genetic liver diseases

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