LIVOGENEA™

Human heterologous hepatocytes transplantation in Hepatic Failure and other liver diseases.

The procedure consists of the followings Standard Operating Procedures:

Collection:

Human Hepatocytes are collected by hepatologist in sterile environment according to a standarized organ rejected procedure. As our knowledge of the species differences in drug metabolism and drug-induced hepatotoxicity has expanded significantly, the need for human-relevant in vitro hepatic ...

Human Hepatocytes are collected by hepatologist in sterile environment according to a standarized organ rejected procedure. As our knowledge of the species differences in drug metabolism and drug-induced hepatotoxicity has expanded significantly, the need for human-relevant in vitro hepatic model systems has become more apparent than ever before. Human hepatocytes have become the "gold standard" for evaluating hepatic metabolism and toxicity of drugs and other xenobiotics in vitro. In addition, they are becoming utilized more extensively for many kinds of biomedical research, including a variety of biological, pharmacological, and toxicological studies. Isolation of primary human hepatocytes from liver tissue obtained from an encapsulated end wedge removed from patients undergoing resection for removal of liver tumors or from resected segments from whole livers obtained from multi-organ donors. In addition, culturing primary hepatocytes under various matrix compositions and geometries, which reestablish intercellular contacts and normal cellular architecture for optimal phenotypic gene expression and response to drugs and other xenobiotics in vitro. Overall, improved isolation, cultivation, and preservation methods have expanded the number of applications for primary human hepatocytes in basic research, which has allowed for exciting advances in our understanding of the biochemical and molecular mechanisms of human liver toxicity and disease.

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Processing:

The liver tissue sample is being coded with a unique barcode for its traceability both during the processing and after the release. Sample processing is being carried out immediately upon receive with validated procedures in a completely closed system (biogenea® set). In particular, the ...

The liver tissue sample is being coded with a unique barcode for its traceability both during the processing and after the release. Sample processing is being carried out immediately upon receive with validated procedures in a completely closed system (biogenea® set). In particular, the hepatocytes are being isolated from liver tissues according to enzymatic procedure. The whole procedure is being carried out in a laminar flow class A/B (Annex I - February 2008 EU guideline for the cGMP standards).

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Quality Control:

A small amount of the hepatocytes culture is controlled for the presence of aerobic and anaerobic germs using the automated blood culture system, while in parallel automated genetic analyzer is used for the detections of HBsAg, as well as for Hepatitis C, HIV Ι/ΙΙ , Toxoplasma , Syphilis and CMV.

Long term Cryopreservation & Product Release:

Only after the completion of all the quality tests isolated hepatocytes are stored in temperatures reaching the (-86C,in these conditions all the metabolic procedures are stopped.Product Release contains a quality certification:
Mean of 10-15x10.6 functional ...

Only after the completion of all the quality tests isolated hepatocytes are stored in temperatures reaching the (-86C,in these conditions all the metabolic procedures are stopped.Product Release contains a quality certification:
Mean of 10-15x10.6 functional heterologous hepatocytes/ KgBW at a rate 1ml/min by percutaneous or transjugular infusion into the portal vein, or injecting into the splenic pulp or the peritoneal cavity

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Clinical Indications:

LIVOGENEA™ is released only according to hospital exception procedure (1394/2007 E.C) to specific liver disorders and failures. Treatment of acute liver failure depends mainly on the stage of the liver damage. In cases of advanced liver damage, liver transplantation (getting a liver from ...

LIVOGENEA™ is released only according to hospital exception procedure (1394/2007 E.C) to specific liver disorders and failures. Treatment of acute liver failure depends mainly on the stage of the liver damage. In cases of advanced liver damage, liver transplantation (getting a liver from another person) is performed. At the time of submission of the application for orphan drug designation, medicinal products to treat symptoms of acute liver failure were authorised. Human heterologous liver cells (for infusion) might be of potential significant benefit for the treatment of acute liver failure because it might improve the long-term outcome of the patients. This assumption will have to be confirmed at the time of marketing authorisation. This will be necessary to maintain the orphan status. Heterologous cells come from donors different to the person who will receive the cells. These liver cells will be isolated and treated so they are suitable used for infusion into patients with acute liver failure. Although the mechanism of action of human heterologous liver cells (for infusion) is not clear, it is believed that when administered in the patient, these human liver cells will support liver function by eliminating toxic metabolites (substances involved in reactions in the body) from the liver.

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