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Hepatocyte Transplantation in the Treatment of Acute Liver Failure: Microencapsulated Hepatocytes Versus Hepatocytes Attached to an Autologous Biomatrix

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A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.
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Keywords: Biomatrix; Bioreactor; Hepatocytes transplantation; Microencapsulated hepatocytes; Model of acute liver failure; Porcine autologous biomatrix

Document Type: Research Article

Affiliations: 1: *Department of Surgical and Gastroenterologic Sciences, Liver Transplant Unit, School of Medicine, University of Padova, Via Giustiniani 2, 35128 Padova, Italy 2: †Department of Pathology, University of Padova, Via A. Gabelli 61, 35128 Padova, Italy 3: ‡Laboratory of Chemical Analysis, University of Padova, Via Giustiniani 2, 35128 Padova, Italy 4: §Department of Nephrology, University of Padova, Via Giustiniani 2, 35128 Padova, Italy 5: ¶Transfusional Unit, University of Padova, Via Giustiniani 2, 35128 Padova, Italy 6: **Department of Histology and Tissue Engineering, University of Padova, Viale G. Colombo 3, 35128 Padova, Italy 7: ††Medical Office, Padova University Hospital 8: #Department of Anesthesiology, University of Padova, Via C. Battisti 267, 35128 Padova, Italy

Publication date: 2003-01-01

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  • Cell Transplantation publishes original, peer-reviewed research and review articles on the subject of cell transplantation and its application to human diseases. To ensure high-quality contributions from all areas of transplantation, separate section editors and editorial boards have been established. Articles deal with a wide range of topics including physiological, medical, preclinical, tissue engineering, and device-oriented aspects of transplantation of nervous system, endocrine, growth factor-secreting, bone marrow, epithelial, endothelial, and genetically engineered cells, among others. Basic clinical studies and immunological research papers are also featured. To provide complete coverage of this revolutionary field, Cell Transplantation will report on relevant technological advances, and ethical and regulatory considerations of cell transplants. Cell Transplantation is now an Open Access journal starting with volume 18 in 2009, and therefore there will be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow work to be disseminated to a wider audience and also entitle the corresponding author to a free PDF, as well as prepublication of an unedited version of the manuscript.

    Cell Transplantation is now being published by SAGE. Please visit their website for the most recent issues.

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