Proliferation and survival of human amniotic epithelial cells during their hepatic differentiation
Stemcells derived from placental tissues are an attractive source of cells for regenerative medicine. Amniotic epithelial cells isolated from human amnion (hAECs) have desirable and competitive characteristics that make them stand out between other stem cells. They have the ability to differentiate...
| Autores: | , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2018 |
| País: | España |
| Institución: | Universidad de Sevilla (US) |
| Repositorio: | idUS. Depósito de Investigación de la Universidad de Sevilla |
| OAI Identifier: | oai:idus.us.es:11441/177047 |
| Acceso en línea: | https://hdl.handle.net/11441/177047 https://doi.org/10.1371/journal.pone.0191489 |
| Access Level: | acceso abierto |
| Palabra clave: | human amniotic epithelial cells Cells |
| Sumario: | Stemcells derived from placental tissues are an attractive source of cells for regenerative medicine. Amniotic epithelial cells isolated from human amnion (hAECs) have desirable and competitive characteristics that make them stand out between other stem cells. They have the ability to differentiate toward all three germ layers, they are not tumorigenic and they have immunosuppressive properties. Although liver transplantation is the best way to treat acute and chronic hepatic failure patients, there are several obstacles. Recently, stem cells have beenspotlighted as alternative source of hepatocytes because of their potential for hepatogenic differentiation. In this work, we aimed to study the proliferation and survival of the hAECsduring their hepatic differentiation. We have also analyzed the changes in pluri potency and hepatic markers. We differentiated amniotic cells applying a specific hepatic differentiation (HD) protocol. We determined by qRT-PCR that hAECs express significant levels of SOX-2, OCT-4 and NANOGduringatleast 15daysinculture and these pluripotent markers diminish during HD. SSEA-4 expression was reduced during HD, measured by immunofluorescence. Morphological characteristics became more similar to hepatic ones in differentiated cells and representative hepatic markers significantly augmented their expres sion, measured by qRT-PCR andWesternblot.Cells achieved a differentiation efficiency of 75%.WeobservedthatHDinducedproliferation and promoted survival of hAECs, during 30 days in culture, evaluated by 3 H-thymidine incorporation and MTT assay. HD also promoted changes in hAECscell cycle. Cyclin D1 expression increased, while p21 and p53 levels were reduced. Immunofluorescence analysis showed that Ki-67 expression was upregu lated during HD. Finally, ERK 1/2 phosphorylation, which is intimately linked to proliferation andcell survival, augmented during all HD process and the inhibition of this signaling path wayaffected not only proliferation but also differentiation. Our results suggest that HD promotes proliferation and survival of hAECs, providing important evidence about the mech anisms governing their hepatic differentiation. We bring new knowledge concerning some of the optimal transplantation conditions for these hepatic like cells. |
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