Meri Huch PhD, Wellcome Trust Research Fellow.
Winner of the 2013 NC3Rs Award 2013
Wellcome-Beit Prize Fellow 2014
University of Cambridge film 'Fighting cancer: animal research at Cambridge' featuring Meri Huch
Stem cells and tissue regeneration in liver and pancreas
How can we repair diseased liver and pancreas? In adult mammals, many tissues have the capacity to self-renew to maintain healthy function and after damage. But the capacity for cell turnover varies. In the intestine and stomach, adult stem cell populations are constantly replenishing, while in the liver and pancreas cell proliferation is limited.
Chronic liver disease and pancreatic cancer are strongly associated with inflammation and tissue damage, which activates stem cells and progenitor cells to repair lost tissue.
Our goal is to understand the activation mechanism in order to harness it for therapeutic strategies. We have established a novel culture system for liver organoids, which allows the massive and infinite expansion of mouse liver cells into three-dimensional structures that resemble functional liver tissue. When transplanted into a mouse model of liver disease (‘FAH –/–’), these cells partially rescued the liver phenotype. We also work with pancreas cells and diseased human liver cells in culture, and are testing how well our models can represent in vivo pathology.
• Aloia L, Mckie MA, Huch M. (2016) Cellular plasticity in the adult liver and stomach. J Physiol. Mar 30. doi: 10.1113/JP271769. [Epub ahead of print]
• Kuijk EW et al (2016) Generation and characterization of rat liver stem cell lines and their engraftment in a rat model of liver failure. Sci Rep. 6:22154.
• Huch M and Dollé L (2016) The plastic cellular states of liver cells: Are EpCAM and Lgr5 fit for purpose? Hepatology. Jan 22. doi: 10.1002/hep.28469. [Epub ahead of print]
• Huch M*, Bonfanti P*, Boj SF*, Sato T*, Loomans CJ, van de Wetering M, Sojoodi M, Li VS, Schuijers J, Gracanin A, Ringnalda F, Begthel H, Hamer K, Mulder J, van Es JH, de Koning E, Vries RG, Heimberg H and Clevers H (2013) Unlimited in vitro expansion of adult bi-potent pancreas progenitors through the Lgr5/R-spondin axis. EMBO J 32(20):2708-21.
• Huch M*, Dorrell C*, Boj SF, van Es JH, Li VSW, van de Wetering M, Sato T, Hamer K, Sasaki N, Finegold MJ, Haft A, Vries R, Grompe M and Clevers H (2013) In vitro expansion of single Lgr5+ liver stem cells induced by Wnt-driven regeneration. Nature 494: 247-50.
• Barker N*, Huch M*, Kujala P, van de Wetering M, Snippert HJ, van Es JH, Sato T, Stange DE, Begthel H, van den Born M, Danenberg E, van den Brink S, Korving J, Abo A, Peters PJ, Wright N, Poulsom R and Clevers H (2010) Lgr5(+ve) stem cells drive self-renewal in the stomach and build long-lived gastric units in vitro. Cell Stem Cell 6(1):25-36.
* Denotes joint first authors.