Gurdon Institute 2016 Prospectus

Page 20

Meritxell Huch 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.

Stem cells and tissue regeneration in liver and pancreas

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. Co-workers: Luigi Aloia, Robert Arnes, Laura Broutier, Lucia Cordero Espinoza, John Crang, Berta Font Cunill, Daisy Harrison, Christopher Hindley, Nicolas Hircq, Gianmarco Mastrogiovanni, Mikel McKie, Cora Olpe Selected publications: Huch M and Koo BK (2015) Modeling mouse and human development using organoid cultures. Development 142(18): 3113–3125. Boj SF et al. (2015) Organoid models of human and mouse ductal pancreatic cancer. Cell 160(1–2): 324–338. Huch M et al. (2015) Long-term culture of genome-stable bipotent stem cells from adult human liver. Cell 160(1–2): 299–312.

18 Focus on research


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