Open Access Consideration of a Safe Protocol for Hepatocyte Transplantation Using Infantile Pigs

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Abstract:

Hepatocyte transplantation is hoped to be an alternative treatment to certain cases of liver transplantation. The most promising indication is for congenital metabolic diseases, especially in infants. To establish a safe protocol for hepatocyte transplantation into infants, we examined physiological changes during treatment using infantile pigs. Recipient pigs (domestic, crossbred with Large-Yorkshire, Landrace, and Duroc; 2.5 kg; 7‐14 days old) were anesthetized with isoflurane; a midline incision of minimum length provided access to the superior mesenteric vein. A double lumen catheter was inserted through the vein to within 1 cm of the hepatic portal region. Physiological parameters such as heart rate, systemic blood pressure, and portal pressure were monitored. Cryopreserved porcine hepatocytes isolated from the same strain were suspended in physiological saline and transfused through the catheter. In experiments requiring tracing, cells were stained with fluorescent dye prior to transfusion. Recipient pigs were kept for 1 day and sacrificed for histological liver examination. After preliminary experiments, the optimized number and concentration for hepatocyte transplantation were determined to be 1 × 108 cells/kg and 1 × 107 cells/ml. The cell suspension was transfused at a rate of 0.67 ml/min. No marked anomaly of physiological parameters was observed, whereas light tachycardia occurred in preliminary trials when the transfusion rate was faster than our standard protocol. All five pigs transfused with the established method recovered from anesthesia and survived with good vital signs. Histology revealed that the transfused hepatocytes were integrated in the hepatic tissue.

Keywords: Hepatocyte transplantation; Infantile pigs; Safe protocol

Document Type: Research Article

DOI: http://dx.doi.org/10.3727/215517912X639469

Publication date: January 1, 2012

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  • The importance of translating original, peer-reviewed research and review articles on the subject of cell therapy and its application to human diseases to society has led to the formation of the journal Cell Medicine. To ensure high-quality contributions from all areas of transplantation, the same rigorous peer review will be applied to articles published in Cell Medicine. Articles may 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, and stem cells, among others. Basic clinical studies and immunological research papers may also be featured if they have a translational interest. To provide complete coverage of this revolutionary field, Cell Medicine will report on relevant technological advances and their potential for translational medicine. Cell Medicine will be a purely online Open Access journal. There will therefore be an inexpensive publication charge, which is dependent on the number of pages, in addition to the charge for color figures. This will allow your work to be disseminated to a wider audience and also entitle you to a free PDF, as well as prepublication of an unedited version of your manuscript.

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