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Meritxell Huch

huchMeri Huch PhD, Wellcome Trust Sir Henry Dale Fellow.

Europe PMC | Pubmed

Winner of the 2013 NC3Rs Award

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

2016 HuchHow 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.

Selected publications:

• 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.

groupHuch2015

Video: Meet Meri Huch

Plain English

The liver is a very slowly dividing organ but, when damaged by toxins present on the food or other environmental agents, it starts the machinery to regenerate itself and bring the organ back to its original resting state. Our aim is to understand the molecular mechanism by which liver or other adult cells sense the damage infringed to the tissue and start the repairing process. Understanding these mechanisms is crucial to improve our knowledge on the basics of cancer initiation, as during tumorigenesis, similar mechanisms have to be put in place to activate the resting cells to start proliferating. 

We are also interested in developing tools to study human physiology and disease in vitro in a petri dish. Because of their numerous biomedical implications in studies of hepatitis, drug testing, as well as transplantation for chronic liver diseases, scientists around the world have unsuccessfully attempted for decades to regenerate primary liver cells. 

We have recently achieved that challenge by establishing a novel liver culture system named 'liver organoid culture' that allows the massive and infinite expansion of mouse liver cells into 3D structures that resemble functional liver tissue in a dish. Of note, when these cells are grown in vitro and transplanted into a mouse model of an inherited liver disease, which resembles the Tyrosinemia type I human liver disease, the cultured and transplanted liver cells continued to grow in the recipient livers and alleviated the pathology of the disease by prolonging the survival of the transplanted mice, thus proving their therapeutic potential.

Co-workers

Luigi Aloia • Robert Arnes • Laura Broutier • Lucia Cordero Espinoza • Nikitas Georgakopoulos • Daisy Harrison • Gianmarco Mastrogiovanni • Mikel McKie • Kathy Oswald • Nicole Prior