Topic 3 : STEM CELL PROJECT

Topics - overview

Title

Project leader

Characterisation of liver stem/progenitor cells,
their niche and potential use as therapeutics

Leo van Grunsven PhD

Postdoc projects

Laurent Dollé PhD

BRUSTEM:
Regenerative medicine of the liver using synergistic mixtures of hepatocytes with mesenchymal stem/progenitor cells or hepatic stellate cells
(2008-2014)

HEPRO:
HEPRO I: The hepatic progenitor cell niche under experimental conditions and in human liver disease
(2007-2011)

HEPRO II: Human liver disease: study of the hepatic stem cells and their niche, and development of novel model systems (2012-2017)

PhD project

Stefaan Verhulst

Liver progenitor cells, their secretome and liver regeneration (2013-2016)

Current Funding

 

Characterisation of liver stem/progenitor cells, their niche and potential use as therapeutics


Hepatic cell therapy is considered as a therapeutic alternative to orthotopic transplantation for several acute or chronic liver diseases. The approach is based on the transfer, via an intact vascular system, of liver cell suspensions into the diseased liver. Although the technique was shown to be feasible and well tolerated in humans, several limitations are still hampering its clinical development such as the scarcity of human liver cells, the in vitro hepatocyte alteration (after primary culture & cryopreservation), the low liver engraftment rate and the durability of transplanted hepatocytes function (1,2). Hence, exploration of alternative sources to mature hepatocytes is mandatory. Because of their potential to self renew and to give rise to highly specialized cells, adult liver progenitor cells (LPCs) may serve as alternative source for the generation of hepatocyte-like cells (3).
In adult livers, LPCs are quiescent stem cells with a low proliferating rate, representing a reserve compartment that is activated only when the mature epithelial cells of the liver are continuously damaged or inhibited in their replication, or in cases of severe cell loss. In the liver, LPCs are found in the canals of Hering (4), a niche that is composed of numerous cells such as HSCs, endothelial cells, hepatocytes, cholangiocytes, Kupffer cells and inflammatory cells. Our ultimate goal is to detect the LPC niche(s) in the injured human liver and to stimulate this niche, and the residing LPCs, without further injury of the liver. LPCs represent only a small portion of the entire liver cell population but can be isolated by using some of their intrinsic properties e.g. size, density, antigenecity and function.

References
1.Sahin, M. B. et al. Liver Transpl 14, 333-45 (2008) 2.Sancho-Bru, P. et al. Gut 58, 594-603 (2009) 3.Duncan, A. W., Dorrell, C. & Grompe, M. Gastroenterology 137, 466-81 (2009) 4.Gaudio, E. et al. Dig Liver Dis 41, 455-62 (2009)

©2004-2014• LIVR • Vrije Universiteit Brussel • Faculteit Geneeskunde & Farmacie • Laarbeeklaan 103 • 1090 Jette • Tel.: 02/477.44.09• jmlazou@vub.ac.be