Abstract
Background: The predisposition of a reliable preclinical in vitro model applicable during early stages of drug development and representative for the human situation in vivo is crucial for the development of new chemical molecules, which are safe and pharmacologically active. This model must be able to screen the safety and the pharmacological effectiveness of such molecules and their metabolites. Previous research of the host lab has shown, at the protein level, that neural crest-derived progenitors, isolated from the dermis, are able to transdifferentiate into hepatic cells in a hepatic stimulated micro-environment. In the present study it was examined whether these changes at the morphological and protein level also can be confirmed at the gene level, using qRT-PCR.Results: Based on the presently obtained results we can carefully deduce that the earlier results, found at the protein level, are confirmed at the gene level. Indeed, specific genes are expressed at well defined stages of the differentiation process, mimicking the liver embryogenesis in vivo. The adult hepatic markers HNF4?, ALB and MRP2 and the biliary marker HNF6 undergo an upregulation during the hepatic differentiation process, whereas (immature) bilairy markers CK19 and Cx43 are downregulated. In conclusion, we can tentatively confirm that upon sequential and gradual exposure to hepatogenic growth factors and cytokines (AVA, BMP4, FGF4, HGF, ITS, Dex, OSM), in accordance with the liver embryogenesis in vivo, hSKP derived hepatic progenitors (OCT4+, NANOG+, cKIT+, Cx43+, CK19+, HNF4?+, HNF6+, C/EBP?+, MRP2+, ALB+) are obtained, that share a similar gene expression pattern with human hepatic progenitors (OCT4+, cKIT+, Cx43+, CK18+, CK19+, HNF4?+, HNF6+, C/EBP?+, ALB+).
| Date of Award | Jul 2010 |
|---|---|
| Original language | English |
| Supervisor | Vera Rogiers (Promotor), Joery De Kock (Co-promotor) & Sarah Snykers (Co-promotor) |
Keywords
- hSKP