Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules
Good quality cryopreserved human hepatocytes are becoming an important source for clinical hepatocyte transplantation. However, the process of cryopreservation leads to both structural and functional impairment of hepatocytes. The aim of this study was to investigate the mechanisms of cryopreservati...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2007-07-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/000000007783465000 |
| _version_ | 1819039521906360320 |
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| author | Claire Terry Robin D. Hughes Ragai R. Mitry Sharon C. Lehec Anil Dhawan |
| author_facet | Claire Terry Robin D. Hughes Ragai R. Mitry Sharon C. Lehec Anil Dhawan |
| author_sort | Claire Terry |
| collection | DOAJ |
| description | Good quality cryopreserved human hepatocytes are becoming an important source for clinical hepatocyte transplantation. However, the process of cryopreservation leads to both structural and functional impairment of hepatocytes. The aim of this study was to investigate the mechanisms of cryopreservation-induced nonattachment in human hepatocytes. Hepatocytes were cryopreserved after isolation from unused donor liver tissue. Cell attachment to collagen-coated plates was measured. A cDNA gene array system for 96 cell adhesion-related molecules was used to determine mRNA expression in fresh and cryopreserved hepatocytes. Two cell adhesion molecule proteins were investigated further: β1-integrin, a cell-matrix adhesion molecule, and E-cadherin, a cell–cell adhesion molecule. Attachment efficiency was significantly decreased after cryopreservation of human hepatocytes. Twenty-two genes were downregulated after cryopreservation including integrins, cadherins, catenins, and matrix metalloproteinases (MMPs). β1-Integrin gene and protein expression were significantly decreased in cultured cryopreserved hepatocytes compared to fresh hepatocytes. There was a significant correlation between loss of β1-integrin and attachment in cryopreserved cells. Degradation of E-cadherin was increased in cryopreserved hepatocytes. The process of cryopreservation leads to downregulation of cell adhesion molecules at the gene and the cellular level. New cryopreservation protocols are needed to prevent these effects on cell attachment. |
| first_indexed | 2024-12-21T08:54:32Z |
| format | Article |
| id | doaj.art-7bd6e7ff883f4e74a91d15fe2250b561 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-21T08:54:32Z |
| publishDate | 2007-07-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-7bd6e7ff883f4e74a91d15fe2250b5612022-12-21T19:09:36ZengSAGE PublishingCell Transplantation0963-68971555-38922007-07-011610.3727/000000007783465000Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion MoleculesClaire Terry0Robin D. Hughes1Ragai R. Mitry2Sharon C. Lehec3Anil Dhawan4Institute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UKInstitute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UKInstitute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UKInstitute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UKInstitute of Liver Studies, King's College London School of Medicine at King's College Hospital, London, UKGood quality cryopreserved human hepatocytes are becoming an important source for clinical hepatocyte transplantation. However, the process of cryopreservation leads to both structural and functional impairment of hepatocytes. The aim of this study was to investigate the mechanisms of cryopreservation-induced nonattachment in human hepatocytes. Hepatocytes were cryopreserved after isolation from unused donor liver tissue. Cell attachment to collagen-coated plates was measured. A cDNA gene array system for 96 cell adhesion-related molecules was used to determine mRNA expression in fresh and cryopreserved hepatocytes. Two cell adhesion molecule proteins were investigated further: β1-integrin, a cell-matrix adhesion molecule, and E-cadherin, a cell–cell adhesion molecule. Attachment efficiency was significantly decreased after cryopreservation of human hepatocytes. Twenty-two genes were downregulated after cryopreservation including integrins, cadherins, catenins, and matrix metalloproteinases (MMPs). β1-Integrin gene and protein expression were significantly decreased in cultured cryopreserved hepatocytes compared to fresh hepatocytes. There was a significant correlation between loss of β1-integrin and attachment in cryopreserved cells. Degradation of E-cadherin was increased in cryopreserved hepatocytes. The process of cryopreservation leads to downregulation of cell adhesion molecules at the gene and the cellular level. New cryopreservation protocols are needed to prevent these effects on cell attachment.https://doi.org/10.3727/000000007783465000 |
| spellingShingle | Claire Terry Robin D. Hughes Ragai R. Mitry Sharon C. Lehec Anil Dhawan Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules Cell Transplantation |
| title | Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules |
| title_full | Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules |
| title_fullStr | Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules |
| title_full_unstemmed | Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules |
| title_short | Cryopreservation-Induced Nonattachment of Human Hepatocytes: Role of Adhesion Molecules |
| title_sort | cryopreservation induced nonattachment of human hepatocytes role of adhesion molecules |
| url | https://doi.org/10.3727/000000007783465000 |
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