Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation
The use of human liver progenitor cells in the development of clinical cell therapy depends on their constant availability and unaltered properties during culture. The present study investigates the effects of long-term in vitro culture on the specific characteristics of these cells and on their gen...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-10-01
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| Series: | Cell Transplantation |
| Online Access: | https://doi.org/10.3727/096368912X639026 |
| _version_ | 1818341524881014784 |
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| author | Isabelle Scheers Cedric Maerckx Dung Ngoc Khuu Sabrina Marcelle Anabelle Decottignies Mustapha Najimi Etienne Sokal |
| author_facet | Isabelle Scheers Cedric Maerckx Dung Ngoc Khuu Sabrina Marcelle Anabelle Decottignies Mustapha Najimi Etienne Sokal |
| author_sort | Isabelle Scheers |
| collection | DOAJ |
| description | The use of human liver progenitor cells in the development of clinical cell therapy depends on their constant availability and unaltered properties during culture. The present study investigates the effects of long-term in vitro culture on the specific characteristics of these cells and on their genetic stability. Adult-derived human liver progenitor cells (ADHLPCs) were isolated from 12 donors and cultured until senescence and cell death. Cells were analyzed at different time points for their phenotype stability and differentiation potential. In addition, growth characteristics, chromosomal karyotype, telomere maintenance mechanisms, and activity of cell cycle-related genes were studied. Finally, their in vivo tumorigenicity was investigated in a xenograft assay. The long-term culture of ADHLPCs revealed a variable proliferation capacity. Cells maintained their original phenotype and acquired hepatocyte-like metabolic functions after differentiation. Eight of the 12 cell populations grew fast (doubling time of 6.3 days) during a limited time period (mean, 116.2 days), and mainly presented normal cytogenetic features. The four other cell cultures presented an early decline in growth potential (doubling time of 28.6 days) and premature senescence. Chromosomal alterations were detected in three of four cultures at passage 6. Cytogenetic anomalies were not correlated with tumorigenic potential in vitro or in vivo, and expression of cell cycle-related genes was appropriately upregulated, inducing senescence. Although chromosomal anomalies may occur in long-term cell cultures, neither transformation nor alteration of their characteristics was noted during in vitro expansion. All ADHLPCs reached senescence and growth arrest. Presenescent ADHLPCs might therefore be considered as a suitable source for liver-based cell therapy. |
| first_indexed | 2024-12-13T16:00:10Z |
| format | Article |
| id | doaj.art-24121452c0774bc0932b5a873154eaa4 |
| institution | Directory Open Access Journal |
| issn | 0963-6897 1555-3892 |
| language | English |
| last_indexed | 2024-12-13T16:00:10Z |
| publishDate | 2012-10-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Cell Transplantation |
| spelling | doaj.art-24121452c0774bc0932b5a873154eaa42022-12-21T23:39:11ZengSAGE PublishingCell Transplantation0963-68971555-38922012-10-012110.3727/096368912X639026Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against TransformationIsabelle Scheers0Cedric Maerckx1Dung Ngoc Khuu2Sabrina Marcelle3Anabelle Decottignies4Mustapha Najimi5Etienne Sokal6Université Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Center for Human Genetics, Brussels, BelgiumUniversité Catholique de Louvain, de Duve Institute, Genetic and Epigenetic Alterations of Genomes Unit, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumUniversité Catholique de Louvain, Institut de Recherche Clinique et Expérimentale (IREC), Laboratory of Pediatric Hepatology and Cell Therapy, Brussels, BelgiumThe use of human liver progenitor cells in the development of clinical cell therapy depends on their constant availability and unaltered properties during culture. The present study investigates the effects of long-term in vitro culture on the specific characteristics of these cells and on their genetic stability. Adult-derived human liver progenitor cells (ADHLPCs) were isolated from 12 donors and cultured until senescence and cell death. Cells were analyzed at different time points for their phenotype stability and differentiation potential. In addition, growth characteristics, chromosomal karyotype, telomere maintenance mechanisms, and activity of cell cycle-related genes were studied. Finally, their in vivo tumorigenicity was investigated in a xenograft assay. The long-term culture of ADHLPCs revealed a variable proliferation capacity. Cells maintained their original phenotype and acquired hepatocyte-like metabolic functions after differentiation. Eight of the 12 cell populations grew fast (doubling time of 6.3 days) during a limited time period (mean, 116.2 days), and mainly presented normal cytogenetic features. The four other cell cultures presented an early decline in growth potential (doubling time of 28.6 days) and premature senescence. Chromosomal alterations were detected in three of four cultures at passage 6. Cytogenetic anomalies were not correlated with tumorigenic potential in vitro or in vivo, and expression of cell cycle-related genes was appropriately upregulated, inducing senescence. Although chromosomal anomalies may occur in long-term cell cultures, neither transformation nor alteration of their characteristics was noted during in vitro expansion. All ADHLPCs reached senescence and growth arrest. Presenescent ADHLPCs might therefore be considered as a suitable source for liver-based cell therapy.https://doi.org/10.3727/096368912X639026 |
| spellingShingle | Isabelle Scheers Cedric Maerckx Dung Ngoc Khuu Sabrina Marcelle Anabelle Decottignies Mustapha Najimi Etienne Sokal Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation Cell Transplantation |
| title | Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation |
| title_full | Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation |
| title_fullStr | Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation |
| title_full_unstemmed | Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation |
| title_short | Adult-Derived Human Liver Progenitor Cells in Long-Term Culture Maintain Appropriate Gatekeeper Mechanisms against Transformation |
| title_sort | adult derived human liver progenitor cells in long term culture maintain appropriate gatekeeper mechanisms against transformation |
| url | https://doi.org/10.3727/096368912X639026 |
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