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Successful isolation of liver progenitor cells by aldehyde dehydrogenase activity in naïve mice
Author(s) -
Dollé Laurent,
Best Jan,
Empsen Christophe,
Mei Jie,
Van Rossen Elke,
Roelandt Philip,
Snykers Sarah,
Najimi Mustapha,
Al Battah Feras,
Theise Neil D.,
Streetz Konrad,
Sokal Etienne,
Leclercq Isabelle A.,
Verfaillie Catherine,
Rogiers Vera,
Geerts Albert,
van Grunsven Leo A.
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.24693
Subject(s) - aldehyde dehydrogenase , progenitor cell , cell sorting , stem cell , hepatocyte , stem cell marker , biology , liver cytology , microbiology and biotechnology , liver regeneration , cell , biochemistry , cancer research , chemistry , regeneration (biology) , enzyme , liver metabolism , in vitro
The role of progenitor cells in liver repair and fibrosis has been extensively described, but their purification remains a challenge, hampering their characterization and use in regenerative medicine. To address this issue, we developed an easy and reproducible liver progenitor cell (LPC) isolation strategy based on aldehyde dehydrogenase (ALDH) activity, a common feature shared by many progenitor cells. We demonstrate that a subset of nonparenchymal mouse liver cells displays high levels of ALDH activity, allowing the isolation of these cells by fluorescence‐activated cell sorting. Immunocytochemistry and qPCR analyses on freshly isolated ALDH + cells reveal an enrichment in cells expressing liver stem cell markers such as EpCAM, CK19, CD133, and Sox9. In culture, the ALDH + population can give rise to functional hepatocyte‐like cells as illustrated by albumin and urea secretion and cytochrome P450 activity. ALDH1A1 expression can be detected in canals of Hering and bile duct epithelial cells and is increased on liver injury. Finally, we showed that the isolation and differentiation toward hepatocyte‐like cells of LPCs with high ALDH activity is also successfully applicable to human liver samples. Conclusion : High ALDH activity is a feature of LPCs that can be taken advantage of to isolate these cells from untreated mouse as well as human liver tissues. This novel protocol is practically relevant, because it provides an easy and nontoxic method to isolate liver stem cells from normal tissue for potential therapeutic purposes. (H EPATOLOGY 2012)