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Publication : Inflammatory Cytokine TNFα Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture.

First Author  Peng WC Year  2018
Journal  Cell Volume  175
Issue  6 Pages  1607-1619.e15
PubMed ID  30500539 Mgi Jnum  J:267423
Mgi Id  MGI:6259319 Doi  10.1016/j.cell.2018.11.012
Citation  Peng WC, et al. (2018) Inflammatory Cytokine TNFalpha Promotes the Long-Term Expansion of Primary Hepatocytes in 3D Culture. Cell 175(6):1607-1619.e15
abstractText  In the healthy adult liver, most hepatocytes proliferate minimally. However, upon physical or chemical injury to the liver, hepatocytes proliferate extensively in vivo under the direction of multiple extracellular cues, including Wnt and pro-inflammatory signals. Currently, liver organoids can be generated readily in vitro from bile-duct epithelial cells, but not hepatocytes. Here, we show that TNFalpha, an injury-induced inflammatory cytokine, promotes the expansion of hepatocytes in 3D culture and enables serial passaging and long-term culture for more than 6 months. Single-cell RNA sequencing reveals broad expression of hepatocyte markers. Strikingly, in vitro-expanded hepatocytes engrafted, and significantly repopulated, the injured livers of Fah(-/-) mice. We anticipate that tissue repair signals can be harnessed to promote the expansion of otherwise hard-to-culture cell-types, with broad implications.
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