Human mesenchymal stem cells (MSCs) are being largely studied for their differentiation potential and immunological
properties. In the present study, we evaluated the ability to reliably differentiate mesenchymal
lineages into hepatocyte-like cells both in vitro and in vivo. For this purpose, we handled
several tissue sources and compared typical MSCs from bone marrow (BM) or umbilical cord, to liver-derived mesenchymal-like cells and to fibroblasts. We observed that hepatocyte differentiation of BM-MSCs was incomplete and variable with elective expression of some specific markers. These mesenchymal-derived hepatocyte-like cells (MDHLCs) were also chimerical in their phenotype as they expressed mesenchymal markers while these were down-regulated. We therefore designed differentiation cocktails with an aim to improve
MDHLC phenotype and some unexpected results were obtained with LIF cytokine whose
action on stem cells for hepatocyte differentiation was not documented. Nevertheless, we observed a limitation in the acquisition yield of hepatic features. Furthermore, the hepatocytelike phenotype of MDHLCs completely disappeared when the cells were incubated into
growth medium. However, we showed that hepatic functionality of these cells, as urea
secretion and gluconeogenesis, could be increased under specific conditions, suggesting the
potential to improve MDHLC phenotype.
In vivo, MSCs were able to express hepatic markers into SCID-mice livers while their
chimerical phenotype remained. In contrast, MDHLCs down-regulated their hybrid phenotype
after transplantation suggesting a beneficial influence of in vitro differentiation step. MSCs
were also able to engraft and even partially differentiate into wild-type mice which was a
strong argument for their low immunogenicity.
Surprisingly, fibroblasts showed highly similar potential than MSCs to differentiate into
hepatocyte-like cells both in vitro an in vivo and these results underlined the difficulty to
accurately distinguish between both cell types using current techniques. Umbilical cord-derived stem cells (UCMSCs) and adult-derived human liver stem cells (ADHLSCs) were different in nature and displayed a native hybrid phenotype while their
differentiation allowed high levels of hepatocyte-like feature acquisition. Together all these
data suggest the current possibility to engineer mesenchymal-derived hepatocyte-like cells
owning specific features acquisition while remaining limited in their commitment. This
highlights the need for further investigations to evidence the usefulness of these mesenchymal
lineages for liver cell therapy.
| Identifer | oai:union.ndltd.org:BICfB/oai:ucl.ac.be:ETDUCL:BelnUcetd-04162008-143421 |
| Date | 24 April 2008 |
| Creators | Lysy, Philippe |
| Publisher | Universite catholique de Louvain |
| Source Sets | Bibliothèque interuniversitaire de la Communauté française de Belgique |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://edoc.bib.ucl.ac.be:81/ETD-db/collection/available/BelnUcetd-04162008-143421/ |
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