Razvan Iacob1,2,3, Vlad Herlea1,2,4, Lorand Savu1,4, Ioana R Florea1,4,5, Veronica M Ilie1,4,5, George Terinte-Balcan6, Mihaela Gherghiceanu6, Mihaela Uta1, Codruta Popa1,3, Speranta Iacob1,2,3, Ioan V Matei4, Cerasela Jardan3, Daniela Lixandru1,3, Simona Dima1,2,4, Irit Meivar-Levy4,7,8, Sarah Ferber4,7,8,9, Irinel Popescu1,2,4. 1. Center of Excellence in Translational Medicine, Fundeni Clinical Institute, Bucharest, 022328, Romania. 2. Center for Digestive Diseases & Liver Transplantation, Fundeni Clinical Institute, Bucharest, 022328, Romania. 3. Department of Cellular and Molecular Biology and Histology, 'Carol Davila' University of Medicine & Pharmacy Bucharest, Bucharest, 020021, Romania. 4. Dia-Cure, Acad. Nicolae Cajal Institute of Medical Scientific Research, Titu Maiorescu University Bucharest, Bucharest, 040441, Romania. 5. Faculty of Biology, University of Bucharest, Bucharest, 030018, Romania. 6. Laboratory of Ultrastructural Pathology, 'Victor Babes' National Institute of Pathology, Bucharest, 050096, Romania. 7. The Sheba Regenerative Medicine, Stem Cell & Tissue Engineering Center, Sheba Medical Center, Tel-Hashomer, 52621, Israel. 8. Orgenesis Ltd, Ness Ziona, 7414002, Israel. 9. Department of Human Molecular Genetics & Biochemistry, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, 6997801, Israel.
Abstract
Background: Liver cells represent an attractive source of cells for autologous regenerative medicine. The present study assesses the liver cells' stability during in vitro expansion, as a prerequisite for therapeutic use. Results: The human liver cell cultures in this study were propagated efficiently in vitro for at least 12 passages. No significant changes in morphology, intracellular ultrastructures and characteristic markers expression were found during in vitro expansion of cells from all analyzed donors. However, expanded cells derived from male donors of >60 years old, lost the Y chromosome. Conclusion: Liver-derived cell cultures adopt a proliferative, stable mesenchymal phenotype, through an epithelial to mesenchymal transition process. The molecular and phenotypic changes of the cells during propagation are uniform, despite the heterogeneity of the different donors. Loss of Y chromosome occurs after cells' propagation in elder male donors.
Background: Liver cells represent an attractive source of cells for autologous regenerative medicine. The present study assesses the liver cells' stability during in vitro expansion, as a prerequisite for therapeutic use. Results: The human liver cell cultures in this study were propagated efficiently in vitro for at least 12 passages. No significant changes in morphology, intracellular ultrastructures and characteristic markers expression were found during in vitro expansion of cells from all analyzed donors. However, expanded cells derived from male donors of >60 years old, lost the Y chromosome. Conclusion: Liver-derived cell cultures adopt a proliferative, stable mesenchymal phenotype, through an epithelial to mesenchymal transition process. The molecular and phenotypic changes of the cells during propagation are uniform, despite the heterogeneity of the different donors. Loss of Y chromosome occurs after cells' propagation in elder male donors.
Entities:
Keywords:
cell therapy; epithelial to mesenchymal transition; liver-derived mesenchymal cells