Alginate microencapsulated hepatocytes optimised for transplantation in acute liver failure
| Autor: | Daniel Soong, Ragai R. Mitry, Nigel Heaton, Celine Filippi, Maria Serena Longhi, Suttiruk Jitraruch, Robin D. Hughes, Christina Philippeos, Anil Dhawan, Sharon C. Lehec |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Cell Physiology
Pathology medicine.medical_specialty medicine.medical_treatment Cell Acute Liver Failure lcsh:Medicine Gastroenterology and Hepatology Liver transplantation Peripheral blood mononuclear cell chemistry.chemical_compound Medicine and Health Sciences medicine Viability assay lcsh:Science Multidisciplinary business.industry Liver Diseases lcsh:R Biology and Life Sciences Cell Biology Molecular biology Liver regeneration Cell Metabolism Transplantation medicine.anatomical_structure chemistry Hepatocyte Galactosamine lcsh:Q business Research Article |
| Zdroj: | PLoS ONE, Vol 9, Iss 12, p e113609 (2014) PLoS ONE Jitraruch, S, Dhawan, A, Hughes, R D, Filippi, C, Soong, D, Philippeos, C, Lehec, S C, Heaton, N D, Longhi, M S & Mitry, R R 2014, ' Alginate microencapsulated hepatocytes optimised for transplantation in acute liver failure ', PL o S One, vol. 9, no. 12, e113609 . https://doi.org/10.1371/journal.pone.0113609 |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0113609 |
| Popis: | Background and Aim: Intraperitoneal transplantation of alginate-microencapsulated human hepatocytes is an attractive option for the management of acute liver failure (ALF) providing short-term support to allow native liver regeneration. The main aim of this study was to establish an optimised protocol for production of alginate-encapsulated human hepatocytes and evaluate their suitability for clinical use. Methods: Human hepatocyte microbeads (HMBs) were prepared using sterile GMP grade materials. We determined physical stability, cell viability, and hepatocyte metabolic function of HMBs using different polymerisation times and cell densities. The immune activation of peripheral blood mononuclear cells (PBMCs) after co-culture with HMBs was studied. Rats with ALF induced by galactosamine were transplanted intraperitoneally with rat hepatocyte microbeads (RMBs) produced using a similar optimised protocol. Survival rate and biochemical profiles were determined. Retrieved microbeads were evaluated for morphology and functionality. Results: The optimised HMBs were of uniform size (583.5±3.3 μm) and mechanically stable using 15 min polymerisation time compared to 10 min and 20 min (p6 cells/ml provided the highest viability. HMBs incubated in human ascitic fluid showed better cell viability and function than controls. There was no significant activation of PBMCs co-cultured with empty or hepatocyte microbeads, compared to PBMCs alone. Intraperitoneal transplantation of RMBs was safe and significantly improved the severity of liver damage compared to control groups (empty microbeads and medium alone; p |
| Databáze: | OpenAIRE |
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